FAM13A as a Novel Hypoxia-Induced Gene in Non-Small Cell Lung Cancer

Several genome-wide association studies (GWASs), have identified that FAM13A and IREB2 loci are associated with lung cancer, but the mechanisms by which these genes contribute to lung diseases susceptibility, especially in hypoxia context, are unknown. Hypoxia has been identified as a major negative factor for tumor progression in clinical observation. It has been suggested, that lower oxygen tension, may modulate the IREB2 and FAM13A activity. However, the role of these genes in hypoxia response has not been explained. To precise the role of these genes in hypoxia response, we analyzed the FAM13A and IREB2 expression, in lung cancer cells in vitro and lung cancer tissue fragments cultured ex vivo. Three cell lines: non-small cell lung cancer (A549, CORL-105), human lung fibroblasts (HL) and 37 lung cancer tissue fragments were analyzed. The expression of IREB2, FAM13A and HIF1α after sustained 72 hours of hypoxia versus normal oxygen concentration were analyzed by TaqMan® Gene Expression Assays and Western Blot. The expression of FAM13A was significantly up-regulated by hypoxia in two lung cancer cell lines (A549, CORL-105, P<0.001), both at the level of protein and mRNA, and in lung cancer tissue fragments (P=0.0004). The IREB2 was down-regulated after hypoxia in A549 cancer cells (P<0.001).

We found that FAM13A overexpression in human lung cancer cell lines overlapped with hypoxia effect on lung cancer tissues. FAM13A is strongly induced by hypoxia and may be identified as a novel hypoxia-induced gene in non-small cell lung cancer.