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

Abstract

N6-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. The 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. RT-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. This 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.