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

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.

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.

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-1α and VEGA-A through interacting with hnRNP, which in turn regulated the RCC cell invasion.

These findings suggested that hypoxia promoted RCC cell invasion through HIF-1α/lncRNA (ENST00000574654.1)/hnRNP/VEGF-A pathway. Targeting this pathway could potentially improve therapeutic outcomes of renal cell carcinoma.