TCF19 up-regulated in hypoxic lung cancer cells attenuates the anti-tumor effects of sodium selenite.

[BACKGROUND] Hypoxia existing inside tumor tissues stimulates proliferation, metastasis and drug resistance of lung cancer. Selenite, an inorganic form of selenium, has been widely confirmed to induce apoptosis of multiple kinds of tumors. However, its therapeutic effects on hypoxic lung cancer were still unclear.

[METHODS] RNA sequencing experiment was carried out to identify the differential expression patterns of transcriptomes in A549 lung cancer cells under nomorxic and hypoxic conditions. siRNA was transfected to knock down the expression of TCF19, and Western blot or qPCR was used to detect gene expression. Cell counting kit 8 was carried out to test the viability of lung cancer cells, while the flow cytometry was used to determine the ratio of apoptosis.

[RESULTS] Compared to normoxia conditions, the genes related to immune regulation, proliferation or reproduction have been identified to be expressed differentially under hypoxia. Among them, TCF19 was increased significantly and exerted a pro-survival function in A549 cells under hypoxia. Further experiment discovered that selenite dose-dependently inhibited the growth of normoxic lung cancer cells, whereas hypoxic cells exhibited partial drug resistance. However, inhibiting TCF19 expression would finally result in the enhancement of selenite-induced apoptosis of hypoxic A549 cells.

[CONCLUSION] All of the results listed above had explored the molecular mechanisms of hypoxic tumor proliferation, which undoubtedly provided TCF19 as a promising synergistic target to treat selenite-resistant hypoxic lung tumors.