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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Yi Zhang, Wei-Long Hong, Zhi-Ming Li, Qi-Yu Zhang, Kang Zeng
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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
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Chen Ge, Changwei Li
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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.

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15,750 View
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