Medical Oncology

, 30:411

MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma

  • Jian Sun
  • Zhaoli Chen
  • Xiaogang Tan
  • Fang Zhou
  • Fengwei Tan
  • Yibo Gao
  • Nan Sun
  • Xiaohui Xu
  • Kang Shao
  • Jie He
Original Paper
  • 978 Downloads

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.

Keywords

microRNA Cell proliferation Apoptosis mTOR Esophageal squamous cell carcinoma Overall survival 

Supplementary material

12032_2012_411_MOESM1_ESM.docx (731 kb)
Supplementary material 1 (DOCX 731 kb)

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Jian Sun
    • 1
  • Zhaoli Chen
    • 1
  • Xiaogang Tan
    • 1
  • Fang Zhou
    • 1
  • Fengwei Tan
    • 1
  • Yibo Gao
    • 1
  • Nan Sun
    • 1
  • Xiaohui Xu
    • 1
  • Kang Shao
    • 1
  • Jie He
    • 1
  1. 1.Department of Thoracic Surgery, Cancer Hospital and InstituteChinese Academy of Medical SciencesBeijingPeople’s Republic of China

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