MiR-99a Inhibits Cell Proliferation and Tumorigenesis through Targeting mTOR in Human Anaplastic Thyroid Cancer

  • Huang, Hou-Gang (Department of Anaesthesiology, Yongchuan Hospital of Chongqing Medical University) ;
  • Luo, Xi (Department of Anaesthesiology, Yongchuan Hospital of Chongqing Medical University) ;
  • Wu, Shuai (Department of Gastrointestinal Surgery, Yongchuan Hospital of Chongqing Medical University) ;
  • Jian, Bin (Department of Gastrointestinal Surgery, Yongchuan Hospital of Chongqing Medical University)
  • Published : 2015.07.13


MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-99a has been reported as a tumor suppressor gene in various human cancers, but its functions in the context of anaplastic thyroid cancer (ATC) remain unknown. In this study, we reported that miR-99a was commonly downregulated in ATC tissue specimens and cell lines with important functional consequences. Overexpression of miR-99a not only dramatically reduced ATC cell viability by inducing cell apoptosis and accumulation of cells at G1 phase, but also inhibited tumorigenicity in vivo. We then screened and identified a novel miR-99a target, mammalian target of rapamycin (mTOR), and it was further confirmed by luciferase assay. Up-regulation of miR-99a would markedly reduce the expression of mTOR and its downstream phosphorylated proteins (p-4E-BP1 and p-S6K1). Similar to restoring miR-99a expression, mTOR down-regulation suppressed cell viability and increased cell apoptosis, whereas restoration of mTOR expression significantly reversed the miR-99a antitumor activity and the inhibition of mTOR/p-4E-BP1/p-S6K1 signal pathway profile. In clinical specimens and cell lines, mTOR was commonly overexpressed and its protein levels were statistically inversely correlated with miR-99a expression. Taken together, our results demonstrated for the first time that miR-99a functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting the mTOR/p-4E-BP1/p-S6K1 pathway in ATC cells. Given these, miR-99a may serve as a novel prognostic/diagnostic and therapeutic target for treating ATC.


MicroRNA-99a;mTOR;anaplastic thyroid cancer


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