Hypoxia is a common feature of the cancer cell microenvironment, promoting angiogenesis, invasion, metabolic reprogramming, resistance to apoptosis, immune suppression, stemness maintenance, and generally poorer clinical prognosis (1). In addition to induced protein factors, long noncoding RNAs (lncRNAs) are important mediators of the hypoxic response. In a recent study, Chao et al. examined the regulation of the NDRG1-OT1 lncRNA in hypoxic breast cancer cells (2). The authors found that NDRG1-OT1 is upregulated in hypoxic conditions in various breast cancer cell lines of different molecular subtypes, and this is driven by HIF-1α and not HIF-2α. Mechanistically, NDRG1-OT1 acts as a sponge for the miR-875-3p microRNA, which was reported to have tumor suppression activity, and was observed to enhance the malignancy of triple-negative MDA-MB-231 cells. Interestingly, NDRG1-OT1 also codes for a small (66 amino acid) peptide, a phenomenon associated with other lncRNAs, though the authors did not report any functional data. In conclusion, the work of Chao et al. presents new insight into the regulation of, and potential oncogenic function of, a key lncRNA in hypoxic breast cancer cells
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- Cell Death Dis. 2022 Sep 20;13(9):807. doi: 10.1038/s41419-022-05253-2.