Long Noncoding RNA SNHG6 Promotes Carcinogenesis by Enhancing YBX1-Mediated Translation of HIF1α in Clear Cell Renal Cell Carcinoma

Abstract

Background: Dysregulated expression of long noncoding RNA SNHG6 plays important roles in the oncogenesis of many human cancers while the function of SNHG6 remains unclear in clear cell renal cell carcinoma (ccRCC). In this study, we aimed to assess the role of SNHG6 in the progression of ccRCC. Methods: RNA-Seq data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatic methods to identify lncRNA dysregulated in ccRCC. The CCK-8, colony formation, Transwell and wound-healing assays were used to assess the biological function of SNHG6 in vitro, and an in vivo xenograft model in nude mice was established. Quantitative real-time PCR and immunohistochemistry (IHC) were used to analyze the expression of SNHG6 in ccRCC tissues. The underlying mechanisms of SNHG6 were investigated using mRNA microarray analyses, Western blotting, RNA pull-down, and RNA immunoprecipitation. Findings: SNHG6 expression was significantly upregulated in ccRCC tissues compared with paired normal renal tissues. High SNHG6 expression was correlated with advanced T stage and poor survival. Further functional experiments demonstrated that knockdown of SNHG6 in ccRCC cells inhibited cell proliferation, migration and invasion in vitro as well as tumor growth and migration in vivo. Mechanistically, SNHG6 bound to YBX1 to act as a complex, thereby enhancing HIF1α translation. Interpretation: SNHG6 promotes ccRCC progression by binding YBX1 and may serve as a novel molecular target for ccRCC therapy. Funding Statement: This work was supported in part by grants from the National Natural Science Foundation of China (No.81903050) and the Science and Technology Commission of Shanghai Municipality (17ZR1417500). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The study was approved by the Human Ethics Committee of the Fudan University Shanghai Cancer Center.