Cancer Research and Treatment

Original Articles

Gastric Carcinogenesis in the miR-222/221 Transgenic Mouse Model: Boram Choi, Jieun Yu, Tae-Su Han, Young-Kook Kim, Keun Hur, Byeong-Cheol Kang, Woo-Ho Kim, Dae-Yong Kim, Hyuk-Joon Lee, V. Narry Kim, Han-Kwang Yang; Cancer Res Treat. 2017;49(1):150-160. Published online June 23, 2016; DOI: https://doi.org/10.4143/crt.2015.462

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Purpose
MicroRNAs (miRNAs) regulate various cellular functions, including development, cell proliferation, apoptosis, and tumorigenesis. Different signatures associated with various tissue types, diagnosis, progression, prognosis, staging, and treatment response have been identified by miRNA expression profiling of human tumors. miRNAs function as oncogenes or as tumor suppressors. The relationship between gastric cancer and miRNA garnered attention due to the high incidence of gastric cancer in Asian countries. miR-222/221 expression increases in gastric tumor tissues. The oncogenic effect of miR-222/221 was previously determined in functional studies and xenograft models. In this study, transgenic mice overexpressing miR-222/221 were generated to confirm the effect of miR-222/221 on gastric carcinogenesis. Materials and Methods At 6 weeks of age, 65 transgenic mice and 53 wild-type mice were given drinking water containing N-nitroso-N-methylurea (MNU) for 5 alternating weeks to induce gastric cancer. The mice were euthanized at 36 weeks of age and histologic analysis was performed.
Results
Hyperplasia was observed in 3.77% of the wild-type mice and in 18.46% of the transgenic mice (p=0.020). Adenoma was observed in 20.75% of the wild-type mice and 26.15% of the transgenic mice (p=0.522). Carcinoma was observed in 32.08% of the wild-type mice and 41.54% of the transgenic mice (p=0.341). The frequency of hyperplasia, adenoma, and carcinoma was higher in transgenic mice, but the difference was statistically significant only in hyperplasia. Conclusion These results suggest that hyperplasia, a gastric pre-cancerous lesion, is associated with miR-222/221 expression but miR-222/221 expression does not affect tumorigenesis itself.

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The Mechanism of miR-222 Targets Matrix Metalloproteinase 1 in Regulating Fibroblast Proliferation in Hypertrophic Scars
Yi Zhang, Wei-Long Hong, Zhi-Ming Li, Qi-Yu Zhang, Kang Zeng
Aesthetic Plastic Surgery.2021; 45(2): 749. CrossRef
Fraser extracellular matrix complex subunit 1 promotes liver metastasis of gastric cancer
Shinichi Umeda, Mitsuro Kanda, Takashi Miwa, Haruyoshi Tanaka, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Suguru Yamada, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera
International Journal of Cancer.2020; 146(10): 2865. CrossRef
Aldehyde dehydrogenase 1, a target of miR‑222, is expressed at elevated levels in cervical cancer
Changde Liu, Yan Zhang, Shanghua Liang, Yuhua Ying
Experimental and Therapeutic Medicine.2020;[Epub] CrossRef
Expression and regulatory role of miRNA-222 in intervertebral disc degeneration (IDD)
Chen Ge, Changwei Li
Biotechnology & Biotechnological Equipment.2019; 33(1): 1553. CrossRef
MicroRNA-222 regulates the viability of fibroblasts in hypertrophic scars via matrix metalloproteinase 1
Yi Zhang, Xiaohua Lin, Li Zhang, Weilong Hong, Kang Zeng
Experimental and Therapeutic Medicine.2017;[Epub] CrossRef

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Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis: Yun-Suhk Suh, Jieun Yu, Byung Chul Kim, Boram Choi, Tae-Su Han, Hye Seong Ahn, Seong-Ho Kong, Hyuk-Joon Lee, Woo Ho Kim, Han-Kwang Yang; Cancer Res Treat. 2015;47(4):718-726. Published online February 2, 2015; DOI: https://doi.org/10.4143/crt.2014.064

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Purpose
The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis.
Materials and Methods
Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse- transcriptase–polymerase chain reaction (RT-PCR) using five AGC patients, and tissue- microarray (TMA) comprising 47 AGC patients.
Results
CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI- 1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393).
Conclusion
DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.

Citations

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WBP5 Expression Influences Prognosis and Treatment Response in Head and Neck Squamous Cell Carcinoma
Eun-jeong Jeong, Eunjeong Kim, Kwang-Yoon Jung, Seung-Kuk Baek, Yeon Soo Kim
Cancers.2025; 17(4): 587. CrossRef
Expression of Serpin Family E Member 1 (SERPINE1) Is Associated with Poor Prognosis of Gastric Adenocarcinoma
Jie Lv, Chunyang Yu, Hanhan Tian, Tao Li, Changhua Yu
Biomedicines.2023; 11(12): 3346. CrossRef
Helicobacter pylori-induced fibroblast-derived Serpin E1 promotes gastric cancer growth and peritoneal dissemination through p38 MAPK/VEGFA-mediated angiogenesis
Wei Cheng, Yonghui Liao, Yuan Xie, Qinrong Wang, Leilei Li, Yuanjia Chen, Yan Zhao, Jianjiang Zhou
Cancer Cell International.2023;[Epub] CrossRef
Analysis of CFTR gene expression as an immunological and prognostic biomarker in pan-cancers
Qi Wang, Shubing Jia, Jie Zheng, Rongwu Xiang, Yong Cui, Jinghai Zhang, Yijia Xu, Mingyi Zhao
Computers in Biology and Medicine.2022; 146: 105614. CrossRef
Interplay of Helicobacter pylori, fibroblasts, and cancer cells induces fibroblast activation and serpin E1 expression by cancer cells to promote gastric tumorigenesis
Xueshu Chen, Wei Chen, Yan Zhao, Qinrong Wang, Wenling Wang, Yining Xiang, Hang Yuan, Yuan Xie, Jianjiang Zhou
Journal of Translational Medicine.2022;[Epub] CrossRef
SERBP1 affects the apoptotic level by regulating the expression and alternative splicing of cellular and metabolic process genes in HeLa cells
Junjie Zhou, Wenhao Chen, Qianwen He, Dong Chen, Chunguang Li, Congqing Jiang, Zhao Ding, Qun Qian
PeerJ.2022; 10: e14084. CrossRef
A qualitative transcriptional signature of recurrence risk for stages II–III gastric cancer patients after surgical resection
Huarong Zhang, Xiangyu Li, Junling Wu, Jiahui Zhang, Haiyan Huang, Yawei Li, Meifeng Li, Shanshan Wang, Jie Xia, Lishuang Qi, Ting Chen, Lu Ao
Journal of Gastroenterology and Hepatology.2021; 36(9): 2501. CrossRef
Weighted correlation network analysis identifies FN1, COL1A1 and SERPINE1 associated with the progression and prognosis of gastric cancer
Qiaoyun Zhao, Jun Xie, Jinliang Xie, Rulin Zhao, Conghua Song, Huan Wang, Jianfang Rong, Lili Yan, Yanping Song, Fangfei Wang, Yong Xie
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H.M.C. Kumara, Addison Poppy, Dasuni Gamage, Erica Pettke, Abhinit Shah, Xiaohong Yan, Vesna Cekic, Richard Whelan
Molecular and Clinical Oncology.2021;[Epub] CrossRef
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C. Ward, P. Cauchy, P. Garcia, J. Frampton, M. A. Esteban, G. Volpe
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microRNA‐501‐5p promotes cell proliferation and migration in gastric cancer by downregulating LPAR1
Xiang Ma, Jiaxi Feng, Ming Lu, Wenjuan Tang, Jianbo Han, XiaGang Luo, Qinghong Zhao, Li Yang
Journal of Cellular Biochemistry.2020; 121(2): 1911. CrossRef
Adipocyte-Derived Leptin Promotes PAI-1-Mediated Breast Cancer Metastasis in a STAT3/miR-34a Dependent Manner
Si-Jing Li, Xiao-Hui Wei, Xiao-Man Zhan, Jin-Yong He, Yu-Qi Zeng, Xue-Mei Tian, Sheng-Tao Yuan, Li Sun
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Bodong Xu, Zhigang Bai, Jie Yin, Zhongtao Zhang
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Role of ion channels in gastrointestinal cancer
Kyle J Anderson, Robert T Cormier, Patricia M Scott
World Journal of Gastroenterology.2019; 25(38): 5732. CrossRef
Clinicopathological and Prognostic Significance of WW Domain Binding Protein 5 Expression in Papillary Thyroid Carcinoma
Yangyang Qian, Zongfu Pan, Zhenying Guo, Xinyang Ge, Guowan Zheng, Jun Cao, Ping Huang, Xin Zhu, Xuhang Zhu, Qingliang Wen, Minghua Ge
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Cystic fibrosis transmembrane conductance regulator—emerging regulator of cancer
Jieting Zhang, Yan Wang, Xiaohua Jiang, Hsiao Chang Chan
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Identification of Potential Key Genes Associated With the Pathogenesis and Prognosis of Gastric Cancer Based on Integrated Bioinformatics Analysis
Xinkui Liu, Jiarui Wu, Dan Zhang, Zhitong Bing, Jinhui Tian, Mengwei Ni, Xiaomeng Zhang, Ziqi Meng, Shuyu Liu
Frontiers in Genetics.2018;[Epub] CrossRef
The Expression and Significance of FAK/PI3K/AKt/mTOR Signaling Pathway Related Proteins in Human Gastric Carcinoma
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World Journal of Cancer Research.2018; 08(03): 113. CrossRef
Proteomic analysis of evodiamine-induced cytotoxicity in thyroid cancer cells
Hui-I Yu, Hsiu-Chuan Chou, Yi-Ching Su, Li-Hsun Lin, Chieh-Hsiang Lu, Hsiang-Hsun Chuang, Yi-Ting Tsai, En-Chi Liao, Yu-Shan Wei, Yi-Ting Yang, Ying-Ray Lee, Hong-Lin Chan
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Arseniy E. Yuzhalin, Su Yin Lim, Anton G. Kutikhin, Alex N. Gordon-Weeks
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Hengchun Zhang, Zhiguo Sun, Yan Li, Dong Fan, Hao Jiang
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Jimin Min, Boram Choi, Tae-Su Han, Hyuk-Joon Lee, Seong-Ho Kong, Yun-Suhk Suh, Tae-Han Kim, Hwi-Nyeong Choe, Woo Ho Kim, Keun Hur, Han-Kwang Yang
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WW domain binding protein 5 induces multidrug resistance of small cell lung cancer under the regulation of miR-335 through the Hippo pathway
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Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion: Yoon Mi Shin, Jieun Yun, Ok-Jun Lee, Hye-Suk Han, Sung-Nam Lim, Jin Young An, Ki Hyeong Lee, Ki Man Lee, Kang Hyeon Choe; Cancer Res Treat. 2014;46(2):178-185. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.178

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Purpose

The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE).

Materials and Methods

Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA).

Results

The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%.

Conclusion

The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.

Citations

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