m6A methyltransferase KIAA1429 accelerates oral squamous cell carcinoma via regulating glycolysis and ferroptosis
Xu Ke, Xiaojuan Dai, Jincheng Yue
Abstract
N6-methyladenosine (m6A) modification acts as the most prevalent modification on eukaryotic RNA, and its function on oral squamous cell carcinoma (OSCC) is still unclear. Here, the present research aimed to explore the novel function of m6A methyltransferase KIAA1429 in OSCC. Results illustrated that KIAA1429 up-regulated in the OSCC samples and cells. Gain/loss functional assays demonstrated that KIAA1429 repressed the ferroptosis of OSCC. Moreover, KIAA1429 positively accelerated the aerobic glycolysis of OSCC, including glucose uptake, lactate production, ATP level and ECAR. Mechanistically, KIAA1429 could install the m6A modification on the PGK1 mRNA, thereby up-regulating the methylated m6A level. Moreover, m6A reader YTHDF1 recognized the m6A modification site of PGK1 mRNA and enhanced its mRNA stability. Thus, KIAA1429 promoted the OSCC aerobic glycolysis and inhibited the ferroptosis of OSCC through YTHDF1-mediated PGK1 mRNA stability. Taken together, these findings reveal a novel insight for KIAA1429 on OSCC via m6A-dependent manner.