title: Loss of PIG3 increases HIF-1α level by promoting protein synthesis via mTOR pathway in renal cell carcinoma cells.
abstract: PIG3 is a target of the tumor suppressor p53 and is thought to be involved in p53-mediated cell apoptosis. Although PIG3 is similar to oxidoreductases involved in generating ROS, whether PIG3 would regulate HIF-1α was never characterized directly. Here we demonstrated that knockdown of PIG3 by transfecting with specific siRNA could increase the expression of HIF-1α in several human cancer cell lines, including CAKI, FTC-133 and A549. It indicates that PIG3 may be involved in the regulation of HIF-1α. Furthermore, we revealed that PIG3-siliencing increased HIF-1α protein level through promoting its protein biosynthesis via mTOR pathway. In addition, the effect of PIG3 on the production of HIF-1α was further related to VEGF secretion and cell migration. PIG3-downregulation increased the secretion of VEGF and promoted the migration of renal cancer cells obviously. Taken together, these data suggest that PIG3 was involved in HIF-1α regulation, and reveal a novel signaling pathway of PIG3/HIF-1α in the regulation of cell migration in renal cell carcinoma.
authors.affiliation: School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou, Zhejiang, China.|Institute of Tumor, Taizhou University, Taizhou, Zhejiang, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Cancer Biology, Provincial Key Lab of Biotherapy in Zhejiang, Sir Runrun Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.|Taizhou Municipal Hospital, Taizhou, Zhejiang, China.
authors.forename: Jin-Ye
authors.initials: JY
authors.lastname: Xu
authors.affiliation: School of Medicine, Taizhou University, Taizhou, Zhejiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Medicine, Taizhou University, Taizhou, Zhejiang, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: School of Medicine, Taizhou University, Taizhou, Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Taizhou Municipal Hospital, Taizhou, Zhejiang, China.|School of Medicine, Taizhou University, Taizhou, Zhejiang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: School of Medicine, Taizhou University, Taizhou, Zhejiang, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Ding
mesh_terms: D000072283:A549 Cells; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C411296:TP53I3 protein, human; C546842:MTOR protein, human
keywords: HIF-1α; PIG3; mTOR; migration; renal cell carcinoma