miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase.
hTERT is the catalytic subunit of the telomerase complex. Elevated expression of hTERT is associated with the expansion and metastasis of gastric tumor. In this study, we aimed to identify novel tumor suppressor miRNAs that restrain hTERT expression. We began our screen for hTERT-targeting miRNAs with a miRNA microarray. miRNA candidates were further filtered by bioinformatic analysis, general expression pattern in different cell lines, gain-of-function effects on hTERT protein and the potential of these effects to suppress hTERT 3' untranslated region (3'UTR) luciferase activity. The clinical relevance of two miRNAs (miR-1207-5p and miR-1266) was evaluated by real-time RT-PCR. The effects of these miRNAs on cell growth, cell cycle and invasion of gastric cancer cells were measured with CCK-8, flow cytometry and transwell assays. Finally, the ability of these miRNAs to suppress the transplanted tumors was also investigated. Fourteen miRNAs were identified using a combination of bioinformatics and miRNA microarray analysis. Of these fourteen miRNAs, nine were expressed at significantly lower levels in hTERT-positive cell lines compared with hTERT-negative cell lines and five could downregulate hTERT protein expression. Only miR-1207-5p and miR-1266 interacted with the 3' UTR of hTERT and the expression levels of these two miRNAs were significantly decreased in gastric cancer tissues. These two miRNAs also inhibited gastric tumor growth in vitro and in vivo. Altogether, miR-1207-5p and miR-1266 were determined to be hTERT suppressors in gastric cancer, and the delivery of these two miRNAs represents a novel therapeutic strategy for gastric cancer treatment.
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
L
L
Chen
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
M-H
MH
Lü
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
D
D
Zhang
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
N-B
NB
Hao
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Y-H
YH
Fan
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Y-Y
YY
Wu
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
S-M
SM
Wang
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
R
R
Xie
Institute of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400037, China.
D-C
DC
Fang
Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400037, China.
H
H
Zhang
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
C-J
CJ
Hu
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
S-M
SM
Yang
D020413:3' Untranslated Regions; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C575047:MIRN1207 microRNA, human; C571915:MIRN1266 microRNA, human; D035683:MicroRNAs; C509186:TERT protein, human; D019098:Telomerase