Methyltransferase‐like 3‐mediated m6A modification of miR‐1908‐5p contributes to nasopharyngeal carcinoma progression by targeting homeodomain‐only protein homeobox

Abstract

AbstractBackgroundN6‐methyladenosine (m6A) modification interacting microRNAs (miRNAs) have been confirmed to participate in nasopharyngeal carcinoma (NPC) progression. This research investigated miR‐1908‐5p's function and regulatory mechanism in the tumorigenesis of NPC via m6A modification and targeting a key gene.MethodsThe levels of miR‐1908‐5p, homeodomain‐only protein homeobox (HOPX), and methyltransferase‐like 3 (METTL3) expressions were detected via RT‐qPCR. The correlation between miR‐1908‐5p and the HOPX/METTL3 axis, as well as their regulatory mechanism, was investigated by dual luciferase reporter, western blotting, and MeRIP assays. Moreover, the bio‐functions of miR‐1908‐5p, HOPX, and METTL3 in NPC were explored through CCK8, transwell, caspase‐3 activity, and xenograft tumor assays.ResultsRT‐qPCR results indicated a miR‐1908‐5p upregulation in NPC. Knocking down miR‐1908‐5p diminished the NPC cell viability and migration in vitro. In vivo, downregulating miR‐1908‐5p repressed NPC cell tumor growth. Moreover, HOPX was specifically targeted by miR‐1908‐5p, and HOPX downregulation led to reversal of the anti‐tumor impact of the miR‐1908‐5p inhibitor against NPC cell malignancy. Also, METTL3 could mediate the m6A modification of miR‐1908‐5p to regulate its influence on NPC cells.ConclusionThis study demonstrated that the METTL3‐mediated m6A modification of miR‐1908‐5p enhanced the tumorigenesis of NPC by targeting HOPX. These findings propose new insights for NPC diagnosis and therapy.