title: MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma.
abstract: 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.affiliation: Department of Thoracic Surgery, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing 100021, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Chen
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Tan
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Fengwei
authors.initials: F
authors.lastname: Tan
authors.forename: Yibo
authors.initials: Y
authors.lastname: Gao
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.forename: Kang
authors.initials: K
authors.lastname: Shao
authors.forename: Jie
authors.initials: J
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C544266:MIRN100 microRNA, human; C561679:MIRN99 microRNA, human; D035683:MicroRNAs; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases