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

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• 作者：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)
  
• 关键词：microRNA ; Cell proliferation ; Apoptosis ; mTOR ; Esophageal squamous cell carcinoma ; Overall survival
• 刊名：Medical Oncology
• 出版年：2013
• 出版时间：March 2013
• 年：2013
• 卷：30
• 期：1
• 全文大小：603KB
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• 作者单位：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. Department of Thoracic Surgery, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing, 100021, People’s Republic of China
  

文摘

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.