Hypoxia promoted renal cell carcinoma cell migration through regulating lncRNA-ENST00000574654.1.

ABSTRACT: BACKGROUND:Hypoxia is common in solid tumor masses that has functional consequences for tumor progression. Previous studies demonstrated that nearly 80% renal cell carcinoma (RCC) are under hypoxia. However, effect and its mechanism of hypoxia on RCC cell invasion remains to be defined. METHODS:The shRNA expression vectors, which were constructed to express a short hairpin RNA against lncRNA and overexpression of lncRNA, were transfected into the RCC cell lines (SW839 and OSRC-2). Levels of lncRNA-ENST00000574654.1, VEGF-A and VEGF-C mRNA and protein were examined by real-time quantitative-fluorescent PCR and Western blot analysis, respectively. The effects of lncRNA silencing and overexpression on cell invasion of SW839 and OSRC-2 cells were evaluated with cell migration assay. RESULTS:Hypoxia significantly stimulated cell invasion in both RCC cell lines (SW839: 2.38 ± 0.19 of normoxia vs 7.83 ± 0.38 of hypoxia, P < 0.05; and OSRC-2: 1.00 ± 0.08 of normoxia vs 5.88 ± 0.32 of hypoxia, P < 0.05). LncRNA microarray analysis found that lncRNA-ENST00000574654.1 was down-regulated under hypoxia. Consistently, over-expression of lncRNA-ENST00000574654.1 resulted in significant blockade of hypoxia-induced RCC migration. Furthermore, expression of lncRNA-ENST00000574654.1 was regulated by HIF-1? and VEGA-A through interacting with hnRNP, which in turn regulated the RCC cell invasion. CONCLUSIONS:These findings suggested that hypoxia promoted RCC cell invasion through HIF-1?/lncRNA (ENST00000574654.1)/hnRNP/VEGF-A pathway. Targeting this pathway could potentially improve therapeutic outcomes of renal cell carcinoma.

SUBMITTER: Che J 

PROVIDER: S-EPMC7407743 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature