FTO-Mediated RNA Hypomethylation of KCTD11 Promotes the Progression of Non-Small Cell Lung Cancer.

Abstract

N6-methyladenosine (m6A) plays a role in tumorigenesis of lung cancer (NSCLC); FTO functions as an oncogene in various cancers. However, the molecular mechanism underlying FTO-promoted lung cancer progression is still unclear. Gene expression was detected using RT-qPCR, western blot, and immunohistochemistry. The behaviors of lung cancer cells were detected using CCK-8, colony formation assay, and transwell assays. MeRIP and luciferase assays were conducted to FTO-mediated RNA hypomethylation. In vivo assays were performed to verify the roles of FTO in NSCLC. High levels of FTO in NSCLC patients predicted poor outcomes. However, FTO knockdown suppressed the proliferation and migration of A549 cells. Mechanically, FTO downregulated KCTD11 expression through promoting the RNA hypomethylation of KCTD11, the expression of which was decreased in NSCLC. KCTD11 knockdown attenuated the effects of FTO and promoted the malignancy of lung cancer. In summary, FTO functions as an oncogene in NSCLC via downregulating KCTD11. Therefore, FTO/KCTD11 can be a novel target for NSCLC.