Polycomb repressive complex 2 (PRC2) is the epigenetic regulator that induces histone H3
lysine 27 methylation (H3K27me3) and silences specific gene transcription. Enhancer of
zeste homolog 2 (EZH2) is an enzymatic subunit of PRC2, and evidence shows that EZH2
plays an essential role in cancer initiation, development, progression, metastasis, and drug
resistance. EZH2 expression is indeed regulated by various oncogenic transcription factors,
tumor suppressor miRNAs, and cancer-associated non-coding RNA. EZH2 activity is also
controlled by post-translational modifications, which are deregulated in cancer. The canonical
role of EZH2 is gene silencing through H3K27me3, but accumulating evidence shows
that EZH2 methlyates substrates other than histone and has methylase-independent
functions. These non-canonical functions of EZH2 are shown to play a role in cancer
progression. In this review, we summarize current information on the regulation and roles
of EZH2 in cancer. We also discuss various therapeutic approaches to targeting EZH2.
Citations
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Inhibition of EZH2 via the STAT3/HOTAIR signalling axis contributes to cell cycle arrest and apoptosis induced by polyphyllin I in human non-small cell lung cancer cells Hok Shing Li, Yao Xu Steroids.2020; 164: 108729. CrossRef
EZH2 overexpression dampens tumor-suppressive signals via an EGR1 silencer to drive breast tumorigenesis Xiaowen Guan, Houliang Deng, Un Lam Choi, Zhengfeng Li, Yiqi Yang, Jianming Zeng, Yunze Liu, Xuanjun Zhang, Gang Li Oncogene.2020; 39(48): 7127. CrossRef
RETRACTED: Exosome-Delivered LncHEIH Promotes Gastric Cancer Progression by Upregulating EZH2 and Stimulating Methylation of the GSDME Promoter Yan Lu, Kaiqing Hou, Mengsen Li, Xiaobin Wu, Shaochun Yuan Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness Ralf Hass, Juliane von der Ohe, Hendrik Ungefroren Cancers.2020; 12(12): 3716. CrossRef
The EZH2–PHACTR2–AS1–Ribosome Axis induces Genomic Instability and Promotes Growth and Metastasis in Breast Cancer Wenhui Chu, Xi Zhang, Lihua Qi, Yenan Fu, Peng Wang, Wei Zhao, Juan Du, Jing Zhang, Jun Zhan, Yunling Wang, Wei-Guo Zhu, Yu Yu, Hongquan Zhang Cancer Research.2020; 80(13): 2737. CrossRef
Inhibition of EZH2 Enhances the Antitumor Efficacy of Metformin in Prostate Cancer Yifan Kong, Yanquan Zhang, Fengyi Mao, Zhuangzhuang Zhang, Zhiguo Li, Ruixin Wang, Jinghui Liu, Xiaoqi Liu Molecular Cancer Therapeutics.2020; 19(12): 2490. CrossRef
Aberrant differential expression of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type, is associated with disease progression and prognosis Jumei Liu, Li Liang, Sixia Huang, Lin Nong, Dong Li, Bo Zhang, Ting Li Human Pathology.2019; 83: 166. CrossRef
Retracted: Long noncoding RNA TALNEC2 plays an oncogenic role in breast cancer by binding to EZH2 to target p57KIP2 and involving in p‐p38 MAPK and NF‐κB pathways Enqi Qiao, Daobao Chen, Qinglin Li, Weiliang Feng, Xingfei Yu, Xiping Zhang, Liang Xia, Ju Jin, Hongjian Yang Journal of Cellular Biochemistry.2019; 120(3): 3978. CrossRef
Interaction of EZH2 and P65 is involved in the arsenic trioxide-induced anti-angiogenesis in human triple-negative breast cancer cells Fei Jiang, Yuan Li, Lu Si, Zengli Zhang, Zhong Li Cell Biology and Toxicology.2019; 35(4): 361. CrossRef
lncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer Mu Xu, Xiaoxiang Chen, Kang Lin, Kaixuan Zeng, Xiangxiang Liu, Xueni Xu, Bei Pan, Tao Xu, Li Sun, Bangshun He, Yuqin Pan, Huiling Sun, Shukui Wang Journal of Hematology & Oncology.2019;[Epub] CrossRef
Genome-wide expression analysis reveals six contravened targets of EZH2 associated with breast cancer patient survival Kanchan Kumari, Biswajit Das, Amit K. Adhya, Arabinda K. Rath, Sandip K. Mishra Scientific Reports.2019;[Epub] CrossRef
LncRNA ADAMTS9-AS2 promotes tongue squamous cell carcinoma proliferation, migration and EMT via the miR-600/EZH2 axis Yingru Li, Quan Wan, Weiwei Wang, Lianxi Mai, Liujuan Sha, Mubarak Mashrah, Zhaoyu Lin, Chaobin Pan Biomedicine & Pharmacotherapy.2019; 112: 108719. CrossRef
New directions in treating peripheral T-cell lymphomas (PTCL): leveraging epigenetic modifiers alone and in combination Helen Ma, Owen A. O’Connor, Enrica Marchi Expert Review of Hematology.2019; 12(3): 137. CrossRef
iPS-Cell Technology and the Problem of Genetic Instability—Can It Ever Be Safe for Clinical Use? Stephen W. Attwood, Michael J. Edel Journal of Clinical Medicine.2019; 8(3): 288. CrossRef
Protein dynamics analysis reveals that missense mutations in cancer‐related genes appear frequently on hinge‐neighboring residues Jan Fehmi Sayılgan, Türkan Haliloğlu, Mehmet Gönen Proteins: Structure, Function, and Bioinformatics.2019; 87(6): 512. CrossRef
Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit Is Required for Uterine Epithelial Integrity Xin Fang, Nan Ni, John P. Lydon, Ivan Ivanov, Kayla J. Bayless, Monique Rijnkels, Qinglei Li The American Journal of Pathology.2019; 189(6): 1212. CrossRef
Prolactin Receptor Signaling Regulates a Pregnancy-Specific Transcriptional Program in Mouse Islets Mark E Pepin, Hayden H Bickerton, Maigen Bethea, Chad S Hunter, Adam R Wende, Ronadip R Banerjee Endocrinology.2019; 160(5): 1150. CrossRef
Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation Jie Zhou, Shuo Huang, Zhongyu Wang, Jiani Huang, Liang Xu, Xuefeng Tang, Yisong Y. Wan, Qi-jing Li, Alistair L. J. Symonds, Haixia Long, Bo Zhu Nature Communications.2019;[Epub] CrossRef
Silencing of microRNA-708 promotes cell growth and epithelial-to-mesenchymal transition by activating the SPHK2/AKT/β-catenin pathway in glioma Yan Chen, Xubin Deng, Weiquan Chen, Pengwei Shi, Mei Lian, Hongxiao Wang, Kewan Wang, Dadi Qian, Dong Xiao, Hao Long Cell Death & Disease.2019;[Epub] CrossRef
EZH2 upregulates the PI3K/AKT pathway through IGF1R and MYC in clinically aggressive chronic lymphocytic leukaemia Subazini Thankaswamy Kosalai, Mohammad Hamdy Abdelrazak Morsy, Nikos Papakonstantinou, Larry Mansouri, Niki Stavroyianni, Chandrasekhar Kanduri, Kostas Stamatopoulos, Richard Rosenquist, Meena Kanduri Epigenetics.2019; 14(11): 1125. CrossRef
Current state of melanoma diagnosis and treatment Lauren E. Davis, Sara C. Shalin, Alan J. Tackett Cancer Biology & Therapy.2019; 20(11): 1366. CrossRef
DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations Chidimma Agatha Akpa, Karsten Kleo, Dido Lenze, Elisabeth Oker, Lora Dimitrova, Michael Hummel, Francesco Bertolini PLOS ONE.2019; 14(8): e0220681. CrossRef
HO-1 promotes resistance to an EZH2 inhibitor through the pRB-E2F pathway: correlation with the progression of myelodysplastic syndrome into acute myeloid leukemia Zhengchang He, Siyu Zhang, Dan Ma, Qin Fang, Liping Yang, Shaoxian Shen, Ying Chen, Lingli Ren, Jishi Wang Journal of Translational Medicine.2019;[Epub] CrossRef
Hematopoietic Differentiation of Human Pluripotent Stem Cells: HOX and GATA Transcription Factors as Master Regulators Khaled Alsayegh, Lorena V. Cortés-Medina, Gerardo Ramos-Mandujano, Heba Badraiq, Mo Li Current Genomics.2019; 20(6): 438. CrossRef
Long non‐coding small nucleolar RNA host genes in digestive cancers Huan Yang, Zheng Jiang, Shuang Wang, Yongbing Zhao, Xiaomei Song, Yufeng Xiao, Shiming Yang Cancer Medicine.2019; 8(18): 7693. CrossRef
Aberrant Expression of EZH2 in Pediatric Patients with Myelodysplastic Syndrome: A Potential Biomarker of Leukemic Evolution Teresa de Souza Fernandez, Tatiana Fonseca Alvarenga, Elaiza Almeida Antônio de Kós, Viviane Lamim Lovatel, Rita de Cássia Tavares, Elaine Sobral da Costa, Cecília de Souza Fernandez, Eliana Abdelhay BioMed Research International.2019; 2019: 1. CrossRef
Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet Victor G. Martinez, Ester Munera-Maravilla, Alejandra Bernardini, Carolina Rubio, Cristian Suarez-Cabrera, Cristina Segovia, Iris Lodewijk, Marta Dueñas, Mónica Martínez-Fernández, Jesus Maria Paramio Frontiers in Genetics.2019;[Epub] CrossRef
Cigarette smoke affects the onco-suppressor DAB2IP expression in bronchial epithelial cells of COPD patients Giulia Anzalone, Giuseppe Arcoleo, Fabio Bucchieri, Angela M. Montalbano, Roberto Marchese, Giusy D. Albano, Caterina Di Sano, Monica Moscato, Rosalia Gagliardo, Fabio L. M. Ricciardolo, Mirella Profita Scientific Reports.2019;[Epub] CrossRef
Stratifying nonfunctional pituitary adenomas into two groups distinguished by macrophage subtypes Garima Yagnik, Martin J. Rutowski, Sumedh S. Shah, Manish K. Aghi Oncotarget.2019; 10(22): 2212. CrossRef
Genome‑wide analysis reveals the emerging roles of long non‑coding RNAs in cancer (Review) Xiaoxia Ren Oncology Letters.2019;[Epub] CrossRef
EZH2 contributes to the response to PARP inhibitors through its PARP-mediated poly-ADP ribosylation in breast cancer H Yamaguchi, Y Du, K Nakai, M Ding, S-S Chang, J L Hsu, J Yao, Y Wei, L Nie, S Jiao, W-C Chang, C-H Chen, Y Yu, G N Hortobagyi, M-C Hung Oncogene.2018; 37(2): 208. CrossRef
Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-d Pei-Pei Kung, Patrick Bingham, Alexei Brooun, Michael Collins, Ya-Li Deng, Dac Dinh, Connie Fan, Ketan S. Gajiwala, Rita Grantner, Hovhannes J. Gukasyan, Wenyue Hu, Buwen Huang, Robert Kania, Susan E. Kephart, Cody Krivacic, Robert A. Kumpf, Penney Khamph Journal of Medicinal Chemistry.2018; 61(3): 650. CrossRef
Nicotine associated breast cancer in smokers is mediated through high level of EZH2 expression which can be reversed by methyltransferase inhibitor DZNepA Kanchan Kumari, Biswajit Das, Amit Adhya, Sanjib Chaudhary, Shantibhusan Senapati, Sandip K. Mishra Cell Death & Disease.2018;[Epub] CrossRef
Long noncoding RNA GAS5 promotes bladder cancer cells apoptosis through inhibiting EZH2 transcription Miao Wang, Chen Guo, Liang Wang, Gang Luo, Chao Huang, Yawei Li, Dong Liu, Fuqing Zeng, Guosong Jiang, Xingyuan Xiao Cell Death & Disease.2018;[Epub] CrossRef
Valproic Acid Promotes Apoptosis and Cisplatin Sensitivity Through Downregulation of H19 Noncoding RNA in Ovarian A2780 Cells Zahre Sajadpoor, Zeinab Amini-Farsani, Hossein Teimori, Mehdi Shamsara, Mohammad Hossein Sangtarash, Payam Ghasemi-Dehkordi, Farrokh Yadollahi Applied Biochemistry and Biotechnology.2018; 185(4): 1132. CrossRef
Epigenetic dysregulation of key developmental genes in radiation‐induced rat mammary carcinomas Kazuhiro Daino, Mayumi Nishimura, Tatsuhiko Imaoka, Masaru Takabatake, Takamitsu Morioka, Yukiko Nishimura, Yoshiya Shimada, Shizuko Kakinuma International Journal of Cancer.2018; 143(2): 343. CrossRef
The role of enhancer of zeste homolog 2: From viral epigenetics to the carcinogenesis of hepatocellular carcinoma Luca Sanna, Irene Marchesi, Mariarosa A. B. Melone, Luigi Bagella Journal of Cellular Physiology.2018; 233(9): 6508. CrossRef
Decreased expression of microRNA-26b in locally advanced and inflammatory breast cancer Qingqing Ding, Yan Wang, Zhuang Zuo, Yun Gong, Savitri Krishnamurthy, Chia-Wei Li, Yun-Ju Lai, Wei Wei, Jing Wang, Ganiraju C. Manyam, Lixia Diao, Xinna Zhang, Feng Lin, William F. Symmans, Li Sun, Chang-Gong Liu, Xiuping Liu, Bisrat G. Debeb, Naoto T. Ue Human Pathology.2018; 77: 121. CrossRef
EZH2 induces the expression of miR-1301 as a negative feedback control mechanism in triple negative breast cancer Qiuju Wu, Zekun Chen, Guihua Zhang, Wenhui Zhou, You Peng, Rong Liu, Ceshi Chen, Jing Feng Acta Biochimica et Biophysica Sinica.2018; 50(7): 693. CrossRef
Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells Ewa Forma, Paweł Jóźwiak, Piotr Ciesielski, Agnieszka Zaczek, Katarzyna Starska, Magdalena Bryś, Anna Krześlak, Gokul M. Das PLOS ONE.2018; 13(6): e0198351. CrossRef
Anti-tumor and anti-metastasis activities of honey bee larvae powder by suppressing the expression of EZH2 Masakatsu Kageyama, Kejuan Li, Shuang Sun, Guoqing Xing, Ran Gao, Zhongfang Lei, Zhenya Zhang Biomedicine & Pharmacotherapy.2018; 105: 690. CrossRef
Epigenetic silencing of tumor suppressor gene CDKN1A by oncogenic long non-coding RNA SNHG1 in cholangiocarcinoma Yang Yu, Mingjiong Zhang, Ni Wang, Quanpeng Li, Jian Yang, Shuai Yan, Xuezhi He, Guozhong Ji, Lin Miao Cell Death & Disease.2018;[Epub] CrossRef
Emerging roles of Myc in stem cell biology and novel tumor therapies Go J. Yoshida Journal of Experimental & Clinical Cancer Research.2018;[Epub] CrossRef
The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p Mu Xu, Xiaoxiang Chen, Kang Lin, Kaixuan Zeng, Xiangxiang Liu, Bei Pan, Xueni Xu, Tao Xu, Xiuxiu Hu, Li Sun, Bangshun He, Yuqin Pan, Huiling Sun, Shukui Wang Molecular Cancer.2018;[Epub] CrossRef
Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer Xuefei Shi, Zhili Liu, Zhicong Liu, Xueren Feng, Feng Hua, Xixian Hu, Bin Wang, Kaihua Lu, Fengqi Nie EBioMedicine.2018; 37: 177. CrossRef
DUXAP8, a pseudogene derived lncRNA, promotes growth of pancreatic carcinoma cells by epigenetically silencing CDKN1A and KLF2 Yifan Lian, Jiebin Yang, Yikai Lian, Chuangxing Xiao, Xuezhen Hu, Hongzhi Xu Cancer Communications.2018; 38(1): 1. CrossRef
EZH2, HIF-1, and Their Inhibitors: An Overview on Pediatric Cancers Marco Papale, Elisabetta Ferretti, Giuseppe Battaglia, Diana Bellavia, Antonello Mai, Marco Tafani Frontiers in Pediatrics.2018;[Epub] CrossRef
Long Noncoding RNA ANRIL Supports Proliferation of Adult T-Cell Leukemia Cells through Cooperation with EZH2 Zaowen Song, Wencai Wu, Mengyun Chen, Wenzhao Cheng, Juntao Yu, Jinyong Fang, Lingling Xu, Jun-ichirou Yasunaga, Masao Matsuoka, Tiejun Zhao, Viviana Simon Journal of Virology.2018;[Epub] CrossRef
MET/ERK and MET/JNK Pathway Activation Is Involved in BCR-ABL Inhibitor-resistance in Chronic Myeloid Leukemia Masanobu Tsubaki YAKUGAKU ZASSHI.2018; 138(12): 1461. CrossRef
EZH2 inhibitors sensitize myeloma cell lines to panobinostat resulting in unique combinatorial transcriptomic changes Taylor Harding, Jessica Swanson, Brian Van Ness Oncotarget.2018; 9(31): 21930. CrossRef
The untold stories of the speech gene, the FOXP2 cancer gene Maria Jesus Herrero, Yorick Gitton Genes & Cancer.2018; 9(1-2): 11. CrossRef
SKP2 loss destabilizes EZH2 by promoting TRAF6-mediated ubiquitination to suppress prostate cancer W Lu, S Liu, B Li, Y Xie, M G Izban, B R Ballard, S A Sathyanarayana, S E Adunyah, R J Matusik, Z Chen Oncogene.2017; 36(10): 1364. CrossRef
Circ100284, via miR-217 regulation of EZH2, is involved in the arsenite-accelerated cell cycle of human keratinocytes in carcinogenesis Junchao Xue, Yang Liu, Fei Luo, Xiaolin Lu, Hui Xu, Xinlu Liu, Lu Lu, Qianlei Yang, Chao Chen, Weimin Fan, Qizhan Liu Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2017; 1863(3): 753. CrossRef
Regulation of cancer epigenomes with a histone-binding synthetic transcription factor David B. Nyer, Rene M. Daer, Daniel Vargas, Caroline Hom, Karmella A. Haynes npj Genomic Medicine.2017;[Epub] CrossRef
Metastatic biomarkers in synovial sarcoma Rosalia de Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi Biomarker Research.2017;[Epub] CrossRef
Interplay of DNA methyltransferase 1 and EZH2 through inactivation of Stat3 contributes to β-elemene-inhibited growth of nasopharyngeal carcinoma cells JingJing Wu, Qing Tang, LiJuan Yang, YuQing Chen, Fang Zheng, Swei Sunny Hann Scientific Reports.2017;[Epub] CrossRef
Regulation of the JMJD3 (KDM6B) histone demethylase in glioblastoma stem cells by STAT3 Maureen M. Sherry-Lynes, Sejuti Sengupta, Shreya Kulkarni, Brent H. Cochran, Anita B. Hjelmeland PLOS ONE.2017; 12(4): e0174775. CrossRef
Modulation of HAT activity by the BRCA2 N372H variation is a novel mechanism of paclitaxel resistance in breast cancer cell lines Woo Sun Kwon, Sun Young Rha, Hei-Cheul Jeung, Tae Soo Kim, Hyun Cheol Chung Biochemical Pharmacology.2017; 138: 163. CrossRef
Expression and inhibition of BRD4, EZH2 and TOP2A in neurofibromas and malignant peripheral nerve sheath tumors Azadeh Amirnasr, Rob M. Verdijk, Patricia F. van Kuijk, Walter Taal, Stefan Sleijfer, Erik A. C. Wiemer, Marta M. Alonso PLOS ONE.2017; 12(8): e0183155. CrossRef
Morphoproteomics, E6/E7 in-situ hybridization, and biomedical analytics define the etiopathogenesis of HPV-associated oropharyngeal carcinoma and provide targeted therapeutic options Robert E. Brown, Syed Naqvi, Mary F. McGuire, Jamie Buryanek, Ron J. Karni Journal of Otolaryngology - Head & Neck Surgery.2017;[Epub] CrossRef
Epigenetic Silencing of miRNA-34a in Human Cholangiocarcinoma via EZH2 and DNA Methylation Hyunjoo Kwon, Kyoungsub Song, Chang Han, Jinqiang Zhang, Lu Lu, Weina Chen, Tong Wu The American Journal of Pathology.2017; 187(10): 2288. CrossRef
The role of EZH2 in overall survival of colorectal cancer: a meta-analysis Laura Vilorio-Marqués, Vicente Martín, Cristina Diez-Tascón, María Francisca González-Sevilla, Tania Fernández-Villa, Emiliano Honrado, Veronica Davila-Batista, Antonio J. Molina Scientific Reports.2017;[Epub] CrossRef
Identification of coexistence of BRAF V600E mutation and EZH2 gain specifically in melanoma as a promising target for combination therapy Huan Yu, Meng Ma, Junya Yan, Longwen Xu, Jiayi Yu, Jie Dai, Tianxiao Xu, Huan Tang, Xiaowen Wu, Siming Li, Bin Lian, Lili Mao, Zhihong Chi, Chuanliang Cui, Jun Guo, Yan Kong Journal of Translational Medicine.2017;[Epub] CrossRef
Decreased expression of JMJD3 predicts poor prognosis of patients with clear cell renal cell carcinoma Jiajun Wang, Li Liu, Qilai Long, Qi Bai, Yu Xia, Wei Xi, Jiejie Xu, Jianming Guo Oncology Letters.2017; 14(2): 1550. CrossRef
Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells Masanobu Tsubaki, Tomoya Takeda, Toshiki Kino, Kazuko Sakai, Tatsuki Itoh, Motohiro Imano, Takashi Nakayama, Kazuto Nishio, Takao Satou, Shozo Nishida Oncotarget.2017; 8(24): 38717. CrossRef
Methylation-mediated silencing of microRNA-211 promotes cell growth and epithelial to mesenchymal transition through activation of the AKT/β-catenin pathway in GBM Weidong Li, Xiaobo Miao, Lingling Liu, Yue Zhang, Xuejun Jin, Xiaojun Luo, Hai Gao, Xubin Deng Oncotarget.2017; 8(15): 25167. CrossRef
Inhibition of enhancer of zeste homolog 2 increases the expression of p16 and suppresses the proliferation and migration of ovarian carcinoma cells in�vitro and in�vivo Fangfang Lu, Hong Xu, Qi Wang, Meiyi Li, Jiahua Meng, Yan Kuang Oncology Letters.2017;[Epub] CrossRef
miR-202 Diminishes TGFβ Receptors and Attenuates TGFβ1-Induced EMT in Pancreatic Cancer Hardik R. Mody, Sau Wai Hung, Rakesh K. Pathak, Jazmine Griffin, Zobeida Cruz-Monserrate, Rajgopal Govindarajan Molecular Cancer Research.2017; 15(8): 1029. CrossRef
TET-Mediated Sequestration of miR-26 Drives EZH2 Expression and Gastric Carcinogenesis Min Deng, Ruixin Zhang, Zhengxi He, Qinwei Qiu, Xihong Lu, Jiang Yin, Hao Liu, Xiaoting Jia, Zhimin He Cancer Research.2017; 77(22): 6069. CrossRef
The role of the polycomb repressive complex pathway in T and NK cell lymphoma: biological and prognostic implications Soo Hee Kim, Woo Ick Yang, Yoo Hong Min, Young Hyeh Ko, Sun Och Yoon Tumor Biology.2016; 37(2): 2037. CrossRef
Interference with endogenous EZH2 reverses the chemotherapy drug resistance in cervical cancer cells partly by up-regulating Dicer expression Liqiong Cai, Zehua Wang, Denghua Liu Tumor Biology.2016; 37(5): 6359. CrossRef
The Ezh2 polycomb group protein drives an aggressive phenotype in melanoma cancer stem cells and is a target of diet derived sulforaphane Matthew L. Fisher, Gautam Adhikary, Dan Grun, David M. Kaetzel, Richard L. Eckert Molecular Carcinogenesis.2016; 55(12): 2024. CrossRef
Problems of glioblastoma multiforme drug resistance A. A. Stavrovskaya, S. S. Shushanov, E. Yu. Rybalkina Biochemistry (Moscow).2016; 81(2): 91. CrossRef
High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer Si-Hyong Jang, Jong Eun Lee, Mee-Hye Oh, Ji-Hye Lee, Hyun Deuk Cho, Kyung-Ju Kim, Sung Yong Kim, Sun Wook Han, Han Jo Kim, Sang Byung Bae, Hyun Ju Lee Journal of Breast Cancer.2016; 19(1): 53. CrossRef
Expression of Mirna-26B in the Diagnosis and Prognosis of Patients with Non-Small-Cell Lung Cancer Li-Peng Jiang, Zhi-Tu Zhu, Chun-Yan He Future Oncology.2016; 12(9): 1105. CrossRef
Targeting NK Cells for Anticancer Immunotherapy: Clinical and Preclinical Approaches Sebastian Carotta Frontiers in Immunology.2016;[Epub] CrossRef
Role of EZH2 histone methyltrasferase in melanoma progression and metastasis Fade Mahmoud, Bradley Shields, Issam Makhoul, Laura F. Hutchins, Sara C. Shalin, Alan J. Tackett Cancer Biology & Therapy.2016; 17(6): 579. CrossRef
Prognostic value of UTX expression in patients with clear cell renal cell carcinoma Jiajun Wang, Li Liu, Wei Xi, Qilai Long, Yiwei Wang, Qi Bai, Yu Xia, Jiejie Xu, Jianming Guo Urologic Oncology: Seminars and Original Investigations.2016; 34(8): 338.e19. CrossRef
Squamous Cell Cancers: A Unified Perspective on Biology and Genetics G. Paolo Dotto, Anil K. Rustgi Cancer Cell.2016; 29(5): 622. CrossRef
Genomic and Epigenomic Alterations in Cancer Balabhadrapatruni V.S.K. Chakravarthi, Saroj Nepal, Sooryanarayana Varambally The American Journal of Pathology.2016; 186(7): 1724. CrossRef
Epigenetic mechanisms of cell adhesion-mediated drug resistance in multiple myeloma Yusuke Furukawa, Jiro Kikuchi International Journal of Hematology.2016; 104(3): 281. CrossRef
Down-Regulation of TSLP After EZH2 Silencing in ESCC Cell Line Gholamreza Karami Madani, Abolfazl Rad, Mohammad Mahdi Forghanifard Journal of Biomedicine.2016;[Epub] CrossRef
High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas Maria Ramaglia, Velia D’Angelo, Adriana Iannotta, Daniela Di Pinto, Elvira Pota, Maria Carmen Affinita, Vittoria Donofrio, Maria Elena Errico, Angela Lombardi, Cristiana Indolfi, Fiorina Casale, Michele Caraglia Cancer Cell International.2016;[Epub] CrossRef
DNA-PK-mediated phosphorylation of EZH2 regulates the DNA damage-induced apoptosis to maintain T-cell genomic integrity Y Wang, H Sun, J Wang, H Wang, L Meng, C Xu, M Jin, B Wang, Y Zhang, Y Zhang, T Zhu Cell Death & Disease.2016; 7(7): e2316. CrossRef
Significance of EZH2 expression in canine mammary tumors Hyun-Ji Choi, Sungwoong Jang, Jae-Eun Ryu, Hyo-Ju Lee, Han-Byul Lee, Woo-Sung Ahn, Hye-Jin Kim, Hyo-Jin Lee, Hee Jin Lee, Gyung-Yub Gong, Woo-Chan Son BMC Veterinary Research.2016;[Epub] CrossRef
Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitabl Rishi G. Vaswani, Victor S. Gehling, Les A. Dakin, Andrew S. Cook, Christopher G. Nasveschuk, Martin Duplessis, Priyadarshini Iyer, Srividya Balasubramanian, Feng Zhao, Andrew C. Good, Robert Campbell, Christina Lee, Nico Cantone, Richard T. Cummings, Emm Journal of Medicinal Chemistry.2016; 59(21): 9928. CrossRef
MiR-101 Targets the EZH2/Wnt/β-Catenin the Pathway to Promote the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells Hongrui Wang, Yake Meng, Quanjun Cui, Fujun Qin, Haisong Yang, Yu Chen, Yajun Cheng, Jiangang Shi, Yongfei Guo Scientific Reports.2016;[Epub] CrossRef
EZH2 mediates lidamycin-induced cellular senescence through regulating p21 expression in human colon cancer cells Ming-Quan Sha, Xiao-Li Zhao, Liang Li, Li-Hui Li, Yi Li, Tian-Geng Dong, Wei-Xin Niu, Li-Jun Jia, Rong-Guang Shao, Yong-Su Zhen, Zhen Wang Cell Death & Disease.2016; 7(11): e2486. CrossRef
Marginal zone lymphoma-derived interfollicular diffuse large B-cell lymphoma harboring 20q12 chromosomal deletion and missense mutation of BIRC3 gene: a case report Joseph Hatem, April M. Schrank-Hacker, Christopher D. Watt, Jennifer J. D. Morrissette, Adam I. Rubin, Ellen J. Kim, Sunita D. Nasta, Mariusz A. Wasik, Agata M. Bogusz Diagnostic Pathology.2016;[Epub] CrossRef
Expression Profile and Function Analysis of LncRNAs during Priming Phase of Rat Liver Regeneration Jun Li, Wei Jin, Yanli Qin, Weiming Zhao, Cuifang Chang, Cunshuan Xu, Klaus Roemer PLOS ONE.2016; 11(6): e0156128. CrossRef
Non-Canonical EZH2 Transcriptionally Activates RelB in Triple Negative Breast Cancer Cortney L. Lawrence, Albert S. Baldwin, Aamir Ahmad PLOS ONE.2016; 11(10): e0165005. CrossRef
Identification of Polycomb Group Protein EZH2-Mediated DNA Mismatch Repair Gene MSH2 in Human Uterine Fibroids Qiwei Yang, Archana Laknaur, Lelyand Elam, Nahed Ismail, Larisa Gavrilova-Jordan, John Lue, Michael P. Diamond, Ayman Al-Hendy Reproductive Sciences.2016; 23(10): 1314. CrossRef
The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway Hiroyoshi Kurihara, Reo Maruyama, Kazuya Ishiguro, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Kei Mitsuhashi, Hisayoshi Igarashi, Miki Ito, Tokuma Tanuma, Yasutaka Sukawa, Kenji Okita, Tadashi Hasegawa, Kohzoh Imai, Hiroyuki Yamamoto, Yasuhisa Shin Oncotarget.2016; 7(11): 12704. CrossRef
The histone methyltransferase EZH2 as a novel prosurvival factor in clinically aggressive chronic lymphocytic leukemia Nikos Papakonstantinou, Stavroula Ntoufa, Elisavet Chartomatsidou, Konstantia Kotta, Andreas Agathangelidis, Lefki Giassafaki, Tzeni Karamanli, Panagiota Bele, Theodoros Moysiadis, Panagiotis Baliakas, Lesley Ann Sutton, Niki Stavroyianni, Achilles Anagno Oncotarget.2016; 7(24): 35946. CrossRef
Proximal and distal regulation of the HYAL1 gene cluster by the estrogen receptor α in breast cancer cells Lydia Edjekouane, Samira Benhadjeba, Maïka Jangal, Hubert Fleury, Nicolas Gévry, Euridice Carmona, André Tremblay Oncotarget.2016; 7(47): 77276. CrossRef
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Characterization and pharmacologic targeting of EZH2, a fetal retinal protein and epigenetic regulator, in human retinoblastoma Mehnaz Khan, Laura L Walters, Qiang Li, Dafydd G Thomas, Jason M L Miller, Qitao Zhang, Andrew P Sciallis, Yu Liu, Brian J Dlouhy, Patrice E Fort, Steven M Archer, Hakan Demirci, Yali Dou, Rajesh C Rao Laboratory Investigation.2015; 95(11): 1278. CrossRef
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Phosphorylation-mediated EZH2 inactivation promotes drug resistance in multiple myeloma Jiro Kikuchi, Daisuke Koyama, Taeko Wada, Tohru Izumi, Peter O. Hofgaard, Bjarne Bogen, Yusuke Furukawa Journal of Clinical Investigation.2015; 125(12): 4375. CrossRef
Overexpression of enhancer of zeste homolog 2 (EZH2) characterizes an aggressive subset of prostate cancers and predicts patient prognosis independently from pre- and postoperatively assessed clinicopathological parameters Nathaniel Melling, Erik Thomsen, Maria Christina Tsourlakis, Martina Kluth, Claudia Hube-Magg, Sarah Minner, Christina Koop, Markus Graefen, Hans Heinzer, Corinna Wittmer, Guido Sauter, Waldemar Wilczak, Hartwig Huland, Ronald Simon, Thorsten Schlomm, Ste Carcinogenesis.2015; 36(11): 1333. CrossRef
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siRNA Silencing EZH2 Reverses Cisplatin-resistance of Human Non-small Cell Lung and Gastric Cancer Cells Wen Zhou, Jian Wang, Wang-Ying Man, Qing-Wei Zhang, Wen-Gui Xu Asian Pacific Journal of Cancer Prevention.2015; 16(6): 2425. CrossRef
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Purpose This study was conducted in order to determine the most cost-effective strategy, in terms of interval and age range, forliver cancer screening in the high-risk population of Korea. Materials and Methods A stochastic modelwas used to simulate the cost-effectiveness ofliver cancer screening by combined ultrasonography and alpha-fetoprotein testing when varying both screening intervals and age ranges. The effectiveness of these screening strategies in the high-risk population was defined as the probability of detecting preclinical liver cancer, and costwas based on the direct cost ofthe screening and confirmative tests. Optimal cost-effectiveness was determined using the incremental cost-effectiveness ratio. Results Among the 36 alternative strategies, one-year or two-year interval screening for men aged between 50 and 80 years, six-month or one-year interval screening for men aged between 40 and 80 years, and six-month interval screening for men aged between 30 and 80 years were identified as non-dominated strategies. For women, identified non-dominated strategies were: one-year interval screening between age 50 and 65 years, one-year or six-month interval screening between age 50 and 80 years, six-month interval screening between age 40 and 80 years, and six-month interval screening between age 30 and 80 years. Conclusion In Korea, a one-year screening interval for men aged 50 to 80 years would be marginally cost-effective. Further studies should be conducted in order to evaluate effectiveness of liver cancer screening, and compare the cost effectiveness of different liver cancer screening programs with a final outcome indicator such as qualityadjusted life-years or disability-adjusted life-years.
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Purpose The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. Materials and Methods Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m2, and the dose of HM30181A was escalated from 30-210 mg/m2. Results A total of twenty-four patients were enrolled. Only one patient experienced a doselimiting toxicity—a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m2 of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m2 and the area under the curve of plasma concentration- time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m2. The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m2. The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m2. Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. Conclusion The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m2.
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Purpose To date, the risk factors for central venous port-related bloodstream infection (CVPBSI) in solid cancer patients have not been fully elucidated. We conducted this study in order to determine the risk factors for CVP-BSI in patients with solid cancer.
Materials and Methods A total of 1,642 patients with solid cancer received an implantable central venous port for delivery of chemotherapy between October 2008 and December 2011 in a single center. CVP-BSI was diagnosed in 66 patients (4%). We selected a control group of 130 patients, who were individually matched with respect to age, sex, and catheter insertion time.
Results CVP-BSI occurred most frequently between September and November (37.9%). The most common pathogen was gram-positive cocci (n=35, 53.0%), followed by fungus (n=14, 21.2%). Multivariate analysis identified monthly catheter-stay as a risk factor for CVP-BSI (p=0.000), however, its risk was lower in primary gastrointestinal cancer than in other cancer (p=0.002). Initial metastatic disease and long catheter-stay were statistically significant factors affecting catheter life span (p=0.005 and p=0.000). Results of multivariate analysis showed that recent transfusion was a risk factor for mortality in patients with CVP-BSI (p=0.047).
Conclusion In analysis of the results with respect to risk factors, prolonged catheter-stay should be avoided as much as possible. It is necessary to be cautious of CVP-BSI in metastatic solid cancer, especially non-gastrointestinal cancer. In addition, avoidance of unnecessary transfusion is essential in order to reduce the mortality of CVP-BSI. Finally, considering the fact that confounding factors may have affected the results, conduct of a well-designed prospective controlled study is warranted.
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Use of catheter with 2-methacryloyloxyethyl phosphorylcholine polymer coating is associated with long-term availability of central venous port Yuuki Iida, Kumiko Hongo, Takanobu Onoda, Yusuke Kita, Yukio Ishihara, Naoki Takabayashi, Ryo Kobayashi, Takeyuki Hiramatsu Scientific Reports.2021;[Epub] CrossRef
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WITHDRAWN: Prevention of peripherally inserted central catheter-related infections in very low-birth-weight infants by using a central line bundle guideline with a standard checklist Chen Yuan, Qing Zhao, Xiaoyan Song, Fei Meng International Journal of Nursing Sciences.2016; 3(1): 50. CrossRef
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Central venous access in oncology: ESMO Clinical Practice Guidelines B. Sousa, J. Furlanetto, M. Hutka, P. Gouveia, R. Wuerstlein, J.M. Mariz, D. Pinto, F. Cardoso Annals of Oncology.2015; 26: v152. CrossRef
Port type is a possible risk factor for implantable venous access port-related bloodstream infections and no sign of local infection predicts the growth of gram-negative bacilli Jui-Feng Hsu, Hsu-Liang Chang, Ming-Ju Tsai, Ying-Ming Tsai, Yen-Lung Lee, Pei-Huan Chen, Wen-Chieh Fan, Yu-Chung Su, Chih-Jen Yang World Journal of Surgical Oncology.2015;[Epub] CrossRef
Purpose The purpose of this study is to evaluate the outcome of low-dose whole brain radiotherapy (WBRT) with tumor bed boost after methotrexate-based chemotherapy in the management of primary central nervous system lymphoma (PCNSL). Materials and Methods We retrospectively analyzed 64 patients with pathologically proven PCNSL between 2000 and 2011. Methotrexate-based chemotherapy with a median of five cycles was followed by radiotherapy to the whole brain and to the initial tumor bed. The median dose to the whole brain and to the tumor bed was 27 Gy (range, 18 to 36 Gy) and 50.4 Gy (range, 45 to 54 Gy), respectively. Results With a median follow-up period of 27 months, 55 patients (85.9%) achieved complete response (CR). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 52.6% and 39.3%, respectively. In univariate analysis, factors associated with OS were age, performance status, involvement of deep structure, and CR to sequential chemoradiotherapy (CRT). These variables remained as significant factors for OS in multivariate analysis. CR to sequential CRT was the only positive factor associated with PFS (p=0.009). Neurologic toxicity was more common in elderly patients older than 60 years (p=0.025). Conclusion Low-dose WBRT with tumor bed boost after methotrexate-based chemotherapy might be an effective method for management of PCNSL.
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Purpose Peritoneal recurrence is one of the most common patterns of recurrence after gastric cancer surgery and it has a poor prognosis despite all efforts. The aim of this study is to evaluate the prognostic impact of early postoperative intraperitoneal chemotherapy (EPIC) after surgery with curative intent for macroscopically serosa-invading gastric cancer patients. Materials and Methods The records of 245 patients under the age of 70 were reviewed. These patients were suffering from macroscopically seroa-invading gastric cancer and they underwent curative surgery from 1995 to 2004 at the Kyungpook National University Hospital, Daegu, Korea. The overall survival, gastric cancer-specific survival, complications, and patterns of recurrence were compared between the patients who were treated with EPIC and those who were not. Results EPIC was administered to 65 patients, and the remaining 180 patients did not receive this treatment. The 5-year overall and gastric cancer-specific survival rates for the EPIC group were 47.4% and 53.1%, respectively, and those for the non-EPIC group were 26.7% and 29.7%, respectively (p=0.012 for overall survival and p=0.011 for gastric cancer-specific survival). The rates of peritoneal recurrence for the EPIC group and the non-EPIC group were 18.5% and 32.2%, respectively (p=0.038). There were no significant differences in the morbidity or mortality between the two groups. Based on a multivariate analysis of the factors with prognostic significance in univariate analyses, EPIC, pathological lymph node metastasis, differentiation, and the extent of gastric resection were independent prognostic factors. Conclusion The use of EPIC to treat gastric cancer patients with macroscopic serosal invasions resulted in better survival rate by reducing the risk of peritoneal recurrence.
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Cancer Res Treat. 2014;46(3):280-287. Published online July 15, 2014
Purpose A newly isolated mediastinal lymph node (LN) or a small pulmonary nodule, which appears during breast cancer surveillance, may pose a diagnostic dilemma with regard to malignancy. We conducted this study to determine which clinical factors were useful for the differentiation of malignant lesions from benign lesions under these circumstances. Materials and Methods We enrolled breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule that arose during surveillance, and whose lesions were pathologically confirmed. Tissue diagnosis was made by mediastinoscopy, video-assisted thoracic surgery or thoracotomy. Results A total of 43 patients were enrolled (mediastinal LN, 13 patients; pulmonary nodule, 30 patients). Eighteen patients (41.9%) were pathologically confirmed to have a benign lesion (benign group), and 25 patients (58.1%) were confirmed to have malignant lesion (malignant group). Between the two groups, the initial tumor size (p=0.096) and N stage (p=0.749) were similar. Hormone receptor negativity was more prevalent in the malignant group (59.1% vs. 40.9%, p=0.048). The mean lesion size was larger in the malignant group than in the benign group (20.8 mm vs. 14.4 mm, p=0.024). Metastatic lesions had a significantly higher value of maximal standardized uptake (mSUV) than that of benign lesions (6.4 vs. 3.4, p=0.021). Conclusion Hormone receptor status, lesion size, and mSUV on positron emission tomography are helpful in the differentiation of malignant lesions from benign lesions in breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule during surveillance.
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Purpose Non-metastatic colorectal cancer patients with diabetes have poor overall survival than those without diabetes. However, the effect of hyperglycemia on survival after diagnosis of metastatic colorectal cancer (CRC) has not been assessed. Therefore, we assessed the impact of hyperglycemia on the survival and infection-related adverse events (AEs) in patients with metastatic CRC. Materials and Methods We reviewed the records of 206 patients with newly diagnosed metastatic CRC who were treated with palliative chemotherapy from March 2000 to December 2012 at Chungbuk National University Hospital. The mean glucose level of each patient was calculated using all available glucose results. Results The mean glucose levels ranged between 76.8 and 303.5 mg/dL, and patients were categorized into quartiles in accordance to their mean glucose level: group 1 (< 106.7 mg/dL), group 2 (106.7-117.2 mg/dL), group 3 (117.3-142.6 mg/dL), and group 4 (> 142.6 mg/dL). The median overall survival for patients in groups 1, 2, 3, and 4 were 22.6, 20.1, 18.9, and 17.9 months, respectively; however, this difference was not statistically significant (p=0.643). Compared with patients in group 1, those in groups 2, 3, and 4 were at a higher risk of infection-related AEs, according to a multivariate analysis (p=0.002). Conclusion Hyperglycemia was not associated with shorter survival; however, it was associated with infection-related AEs in patients with newly diagnosed metastatic CRC receiving palliative chemotherapy.
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Purpose Interleukin-17 (IL-17) is a proinflammatory cytokine that plays important roles in inflammation, autoimmunity, and cancer. The purpose of this study was to determine if IL-17 indirectly regulates macrophage differentiation through up-regulation of cyclooxygenase-2 (COX-2) expression in the cancer cell lines. Materials and Methods Human cervical cancer HeLa, human lung cancer A549, and mouse prostate cancer Myc-CaP/CR cell lines were treated with recombinant IL-17; Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction analysis were utilized to examine the cellular responses. Results IL-17 up-regulated expression of COX-2 mRNA and protein in HeLa, A549, and Myc- CaP/CR cell lines. IL-17’s effects were mediated through nuclear factor-κB and ERK1/2 signaling pathways as the inhibitors of these pathways could inhibit IL-17- induced COX-2 expression. The conditional medium obtained from the cancer cells contained prostaglandin E2, the levels of which were increased by IL-17 treatment. When treated with the conditional medium, particularly with the IL-17-induced conditional medium, mouse RAW264.7 macrophages and human THP-1 monocytes expressed higher levels of IL-10 (a marker of M2 macrophages) than inducible nitric oxide synthase or tumor necrosis factor α (markers of M1 macrophages). In contrast, when RAW264.7 and THP-1 cells were treated directly with IL-17, expression of these marker genes was not markedly changed. Conclusion The results of this study suggest that IL-17 indirectly promotes M2 macrophage differentiation through stimulation of the COX-2/PGE2 pathway in the cancer cells, thus IL-17 plays an indirect role in regulating the tumor immune microenvironment.
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