Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth Journal Article


Authors: He, X. P.; Shao, Y.; Li, X. L.; Xu, W.; Chen, G. S.; Sun, H. H.; Xu, H. C.; Xu, X.; Tang, D.; Zheng, X. F.; Xue, Y. P.; Huang, G. C.; Sun, W. H.
Article Title: Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth
Abstract: Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. It has been demonstrated that COX-2 overexpression depends on different cellular pathways, involving both transcriptional and post-transcriptional regulation. MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators. Here, we characterize miR-101 expression and its role in the regulation of COX-2 expression, which in turn, will provide us with additional insights into the potential therapeutic benefits of exogenous miR-101 for treatment of gastric cancer. Our results showed that miR-101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue (P < 0.01). Furthermore, lower levels of miR-101 were associated with increased tumor invasion and lymph node metastasis (P < 0.05). We also found an inverse correlation between miR-101 and COX-2 expression in both gastric cancer specimens and cell lines. Significant decreases in COX-2 mRNA and COX-2 levels were observed in the pre-miR-101-infected gastric cancer cells. One possible mechanism of interaction is that miR-101 inhibited COX-2 expression by directly binding to the 3'-UTR of COX-2 mRNA. Overexpression of miR-101 in gastric cancer cell lines also inhibited cell proliferation and induced apoptosis in vitro, as well as inhibiting tumor growth in vivo. These results collectively indicate that miR-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target. COX-2 plays important role in the carcinogenesis and progression of gastric cancer. We found an inverse correlation between miR-101 and COX-2 expression in gastric cancer specimens and cell lines. Overexpression of miR-101 inhibited cell proliferation in vitro and tumor growth in vivo, suggesting that miR-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target. © 2012 The Authors Journal compilation © 2012 FEBS.
Keywords: adult; clinical article; controlled study; human tissue; protein expression; middle aged; cancer growth; nonhuman; drug targeting; lymph node metastasis; lymphatic metastasis; adenocarcinoma; cell proliferation; mouse; animals; mice; animal tissue; gene overexpression; apoptosis; microrna; adenocarcinoma, mucinous; carcinoma, papillary; animal experiment; animal model; cancer cell culture; in vitro study; cell line, tumor; mice, inbred balb c; carcinogenesis; cancer invasion; cancer inhibition; blotting, western; gene expression regulation, neoplastic; correlation analysis; transcription regulation; molecular sequence data; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; cyclooxygenase 2; cell movement; stomach cancer; base sequence; down regulation; 3' untranslated region; tumor growth; micrornas; sequence homology, nucleic acid; cell adhesion; stomach neoplasms; carcinoma, signet ring cell; rna binding; 3' untranslated regions; gastric cancer; cyclooxygenase-2; real-time polymerase chain reaction; mir-101; microrna 101
Journal Title: FEBS Journal
Volume: 279
Issue: 22
ISSN: 1742-464X
Publisher: Blackwell Publishing  
Date Published: 2012-11-01
Start Page: 4201
End Page: 4212
Language: English
DOI: 10.1111/febs.12013
PROVIDER: scopus
PUBMED: 23013439
DOI/URL:
Notes: --- - "Export Date: 3 December 2012" - "CODEN: FJEOA" - "Source: Scopus"
Altmetric
Citation Impact
MSK Authors
  1. Guochang Huang
    15 Huang