Journal
CANCER LETTERS
Volume 360, Issue 2, Pages 151-159Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.01.044
Keywords
miR-1182; hTERT; Gastric cancer; Proliferation; Metastasis
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Funding
- National Natural Science Foundation of China [81272689]
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In humans, telomerase reverse transcriptase (hTERT) determines the activity of telomerase. hTERT is an ideal anticancer target because it is universally expressed in cancer cells and plays a crucial role in carcinogenesis. In this study, we report the miR-1182-mediated post-transcriptional regulation of hTERT. Over-expression of miR-1182 in different gastric cancer cells decreased hTERT protein levels. Bioinformation and dual-luciferase assays revealed that miR-1182 modulated hTERT by binding to its open reading frame (ORF), and this miRNA recognizes elements in the nucleotide region between 2695 and 2719 of hTERT mRNA. Over-expression of hTERT by transfecting pIRES2-hTERT into U2OS cells was abolished by miR-1182, while pIRES2-hTERT-MT, in which miR-1182 target site was synonymously mutated, failed to respond to miR-1182. Further investigation revealed that miR-1182 inhibited gastric cancer proliferation and migration by targeting the ORF1 of hTERT. We also found that miR-1182 could attenuate the proliferative and metastatic potential of SGC-7901 cell in vivo. Moreover, we found a statistically significant inverse correlation between miR-1182 and hTERT protein levels in tissues from 42 gastric cancer patients. These data indicate that miR-1182 suppresses TERT, and thus it could be an effective target for the treatment of gastric cancer. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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