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MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma.
MedLine Citation:
PMID:  23292834     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Recently, microRNA-99 family members, such as miR-99a/b and miR-100, have been reported to exhibit abnormal expression in various malignant tumors, but their functions in carcinomas are controversial. In this study, we focused on miR-99a and miR-100, which were determined to be universally downregulated in esophageal squamous cell carcinoma, and investigated their functions and potential mechanisms of action. The downregulation of miR-99a/100 was validated by qRT-PCR in 101 ESCC surgical tissue samples and in 3 ESCC cell lines. The overexpression of miR-99a and miR-100 via the transient transfection of the corresponding precursor molecules inhibited cell proliferation by inducing apoptosis in the ESCC cell lines. To investigate the molecular mechanism of miR-99a/100-induced apoptosis, luciferase reporter assays and Western blots were performed to demonstrate that the overexpression of miR-99a/100 suppressed the expression of mTOR by directly targeting its 3'UTR in a post-transcriptional manner. Clinically, the decreased expression of miR-99a/100 was associated with worse overall survival in ESCC patients. In conclusion, these results indicated that miR-99a and miR-100 inhibited cell proliferation by suppressing mTOR in ESCC cell lines, and therefore, the miR-99a/100-mTOR signaling pathway is a potential therapeutic target for inducing apoptosis to combat ESCC.
Authors:
Jian Sun; Zhaoli Chen; Xiaogang Tan; Fang Zhou; Fengwei Tan; Yibo Gao; Nan Sun; Xiaohui Xu; Kang Shao; Jie He
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Publication Detail:
Type:  Journal Article     Date:  2013-01-05
Journal Detail:
Title:  Medical oncology (Northwood, London, England)     Volume:  30     ISSN:  1559-131X     ISO Abbreviation:  Med. Oncol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9435512     Medline TA:  Med Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  411     Citation Subset:  IM    
Affiliation:
Department of Thoracic Surgery, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing, 100021, People's Republic of China.
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