microRNA-153 Targets mTORC2 Component Rictor to Inhibit Glioma Cells.
Rictor upregulation and mTORC complex 2 (mTORC2) over-activation participate in glioma cell progression, yet the underling mechanisms are not known. We here identified microRNA-153 (miR-153) as a potential anti-Rictor miRNA, which was downregulated in multiple human glioma tissues and glioma cell lines (U87MG, T98G, U373MG and U251MG). miR-153 downregulation was correlated with Rictor (mRNA and protein) upregulation and p-Akt Ser473 (the mTORC2 indicator) over-activation in the glioma tissues and cells. Our in vitro evidences suggested that Rictor could be one primary target of miR-153 in glioma cells. Exogenous overexpression of miR-153 downregulated Rictor (mRNA and protein) and decreased p-Akt Ser473 in U87MG cells, leading to significant growth inhibition and apoptosis activation. Notably, U87MG cells with Rictor shRNA knockdown showed similar phenotypes of cells with miR-153 overexpression. More importantly, in Rictor-silenced U87MG cells, miR-153 expression failed to further affect cell growth nor apoptosis. In vivo, we showed that miR-153 overexpression dramatically inhibited U87MG tumor growth in nude mice. Together, these results suggest that miR-153 downregulation could be one important reason of Rictor upregulation and mTORC2 over-activation in glioma cells. Further, miR-153-induced anti-glioma cell activity is possibly via downregulating Rictor.
Department of Neurosurgery, the Second Xiangya Hospital of Central South University, Chang Sha, 410011,China.
Yan
Y
Cui
Department of Neurosurgery, the Second Xiangya Hospital of Central South University, Chang Sha, 410011,China.|Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
Jizong
J
Zhao
Department of Neurosurgery, the Second Xiangya Hospital of Central South University, Chang Sha, 410011,China.
Lei
L
Yi
Department of Neurosurgery, the Second Xiangya Hospital of Central South University, Chang Sha, 410011,China.
Yugang
Y
Jiang
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D002352:Carrier Proteins; C556500:MIRN153 microRNA, human; D035683:MicroRNAs; D046912:Multiprotein Complexes; C492571:RICTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases