ALKBH5 Accelerates the Progression of Head and Neck Squamous Cell Carcinoma by Decreasing Methylation of the lncRNA...

Although N6-methyladenosine (m6A) demethylase alkylation repair homolog protein 5 (ALKBH5) is closely associated with the aggressiveness of head and neck squamous cell carcinoma (HNSCC), the underlying molecular mechanisms remain to be fully elucidated. In this study, we screened out a novel ALKBH5/lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1)/miR-654-3p/HOXA10 axis that participated in the regulation of HNSCC development. Specifically, lncRNA NEAT1 was found to be highly expressed in HNSCC tissues and cells, and deletion of NEAT1 suppressed cell proliferation and tumorigenesis, and promoted apoptosis and autophagy to hamper cancer progression in HNSCC. Mechanistic experiments verified that the stability and expressions of NEAT1 were positively regulated by ALKBH5-mediated m6A demethylation, and ALKBH5 deletion induced a suppressive effect on HNSCC cell malignancies were all abrogated by overexpressing NEAT1. In addition, we evidenced that NEAT1 promoted Homeobox A10 (HOXA10) expression via sponging miR-654-3p in a competing endogenous RNA (ceRNA)-dependent manner, and both miR-654-3p inhibition and HOXA10 overexpression recovered cancer malignancies in the NEAT1-deficient HNSCC cells. Taken together, we concluded that ALKBH5-induced m6A demethylation increased the stability and expression levels of NEAT1, and elevated NEAT1 facilitated cancer progression in HNSCC through regulating the downstream miR-654-3p/HOXA10 axis. This study provided potential biomarkers for the diagnosis, treatment and prognosis of HNSCC in clinic.