MiR-99a-5p inhibits bladder cancer cell proliferation by directly targeting mammalian target of rapamycin and predicts patient survival

J Cell Biochem. 2019 Dec;120(12):19330-19337. doi: 10.1002/jcb.27318. Epub 2018 Dec 17.


Bladder cancer is a common malignancy and miR-99a-5p has been reported to be downregulated in bladder cancer, but its function and the underlying mechanism in bladder cancer development remains largely unclear. Here, we report that miR-99a-5p expression was decreased in bladder cancer compared with the adjacent normal tissues. Receiver operating characteristic curve revealed that miR-99a-5p expression signature had area under curve value of 0.7989 in differing bladder cancer from the adjacent normal tissues. Bladder cancer patients with low expression of miR-99a-5p had a poor survival rate. Gain-of-function and loss-of-function approaches demonstrated that miR-99a-5p inhibited bladder cell proliferation and cell cycle. Furthermore, we identified that mammalian target of rapamycin (mTOR) was a direct target of miR-99a-5p and mTOR restore could rescue the proliferative ability of bladder cancer cells. Moreover, miR-99a-5p/mTOR axis regulated S6K1 phosphorylation. These suggested that miR-99a-5p/mTOR axis might be a therapeutic target for bladder cancer.

Keywords: S6K1; bladder cancer; cell proliferation; mammalian target of rapamycin; miR-99a-5p.

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Phosphorylation / genetics
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics*
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology


  • MIRN99 microRNA, human
  • MicroRNAs
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 1