title: miR-1182 attenuates gastric cancer proliferation and metastasis by targeting the open reading frame of hTERT.
abstract: 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.
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Dan
authors: D
authors: Zhang
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Yu-Feng
authors: YF
authors: Xiao
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Jian-Wei
authors: JW
authors: Zhang
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Rui
authors: R
authors: Xie
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Chang-Jiang
authors: CJ
authors: Hu
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Bo
authors: B
authors: Tang
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Su-Min
authors: SM
authors: Wang
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Yu-Yun
authors: YY
authors: Wu
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: 357043808@qq.com.
authors: Ning-Bo
authors: NB
authors: Hao
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: shimingyang@yahoo.com.
authors: Shi-Ming
authors: SM
authors: Yang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011499:Protein Processing, Post-Translational; D038621:Regulatory Sequences, Ribonucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C000597776:MIRN1182 microRNA, human; D035683:MicroRNAs; D038621:Regulatory Sequences, Ribonucleic Acid; C509186:TERT protein, human; D019098:Telomerase
keywords: Gastric cancer; Metastasis; Proliferation; hTERT; miR-1182