Long non-coding RNA HIF1A-AS2 promotes carcinogenesis by enhancing Gli1-mediated HIF1α expression in clear cell renal cell carcinoma.

ABSTRACT

BACKGROUND: The most common urologic tumor in humans with the highest incidence rate is clear cell renal cell carcinoma (ccRCC). Long non-coding RNAs (lncRNAs) act as regulatory factors in several tumors. Here, we studied ccRCC regulated by hypoxia-inducible factor 1α (HIF1α)-antisense RNA 2 (AS2) or HIF1A-AS2. METHODS: We performed wound-healing, transwell, and CCK-8 assays by decreasing or increasing the HIF1A-AS2 expression in RCC cell lines. Western blotting and qRT-PCR were used to identify the expression of downstream genes of the HIF1A-AS2 pathway. Gli1 and HIF1A-AS2 relationship was assessed using RIP and RNA pull-down assays. Lastly, transcriptome sequencing was performed on kidney cancer cells that had been knocked down to find possible regulatory mechanisms. RESULTS: Our results suggest that high expression of HIF1A-AS2 may promote RCC cell proliferation and Gli1 expression as a downstream factor. Furthermore, they have physical binding sites and together regulate HIF1α to encourage the development of ccRCC. HIF1A-AS2 lncRNA may offer a new molecular target for ccRCC treatment. CONCLUSION: lncRNA HIF1A-AS2 affects ccRCC development by regulating HIF1a expression through Gli1.