Downregulation of the long non-coding RNA MDL1AS alters metabolism, differentiation and radiosensibility in NTERA2 and SH-SY5Y cells
Non-coding RNAs provide new chances of targeting multiple oncogenic pathways. Many long non-coding RNAs (lncRNAs) are being characterized as relevant in cancer initiation, progression and recurrence. Therefore, in the present study we studied the effects of mitochondrial D-loop 1 antisense lncRNA (MDL1AS) downregulation on the cellular behavior of NTERA2 and SH-SY5Y cell lines. We found that MDL1AS reduction inhibited oxidative phosphorylation in NTERA2 cells and induced neuritic differentiation in SH-SY5Y cells. This downregulation also produced a strong DNA damage response (DDR) and an increased apoptotic signature by RNAseq analysis, and decreased proliferation in both cell lines. It also differently affected the radiosensibility of these cells, increasing it in SH-SY5Y while decreasing it in NTERA2 cells. These results show that MDL1AS reduction can modulate radiosensibility, metabolism and differentiation in a cell type-specific manner. Furthermore, MDL1AS may constitute a predictive biomarker and a molecular target for new therapies.