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LncRNA GAS6 antisense RNA 1 facilitates the tumorigenesis of clear cell renal cell carcinoma by regulating the AMP-activated protein kinase/mTOR signaling pathway
Authors:Xiaoyun Guo  Hongjun Li  Mei Zhang  Rong Li
Affiliation:1.Department of Nephrology, The Second Hospital of Tianjin Medical University, Hexi, Tianjin 300201, P.R. China;2.Department of Infectious Diseases and Immunology, The Second Hospital of Tianjin Medical University, Hexi, Tianjin 300201, P.R. China;3.Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Hexi, Tianjin 300201, P.R. China
Abstract:The role of GAS6 antisense RNA 1 (GAS6-AS1) in clear cell renal cell carcinoma (ccRCC) remains unclear. The aim of the present study was to investigate the role and molecular mechanisms of GAS6-AS1 in the progression of ccRCC. GAS6-AS1 was found to be upregulated in ccRCC tissues and cell lines, and patients with high GAS6-AS1 expression levels exhibited a poor prognosis. Small interfering (si)RNA GAS6-AS1 inhibited the activity, colony formation, invasiveness and glycolysis of OSRC-2 and SW839 cells, while GAS6-AS1 overexpression promoted these functions. Moreover, si-GAS6-AS1 increased the phosphorylation level of AMP-activated protein kinase (AMPK) and decreased that of mTOR, as well as decreasing proliferating cell nuclear antigen (PCNA), MMP-2 and hexokinase-2 (HK2) expression, which were reversed by inhibiting AMPK or mTOR. In addition, the silencing of GAS6-AS1 suppressed the growth of xenografted tumors and attenuated the expression of PCNA, MMP-2 and HK2 in tumor tissues. These findings conclude that GAS6-AS1 regulated the proliferation, invasiveness and glycolysis of ccRCC cells by regulating the AMPK/mTOR signaling pathway, and suggest that GAS6-AS1 may be a potential therapeutic target for ccRCC.
Keywords:clear cell renal cell carcinoma   GAS6 antisense RNA 1   AMP-activated protein kinase/mTOR signaling pathway   proliferation   glycolysis
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