WTAP accelerates keloids formation by mediating m6A modification of HOXA5 to suppress p53 pathway

Background N6-methyladenosine (m6A) modification has been identified to participate in cancer progression. However, the function of m6A modification in keloid, a kind of fibrous benign tumor, is still not fully explored. This study aimed to explore the function and mechanism of a m6A methyltransferase Wilm's tumor 1–associating protein (WTAP) in keloids formation. Methods The levels of WTAP and Homeobox A5 (HOXA5) in keloids were confirmed by qRT-PCR or western blotting analysis. The change of human keloid fibroblasts (HKFs) cell function was verified by CCK8, wound healing, and transwell assays. Besides, the m6A modification of HOXA5 caused by WTAP was determined by MeRIP assay. Results WTAP was upregulated in keloids, whereas HOXA5 was downregulated in keloids. Upregulating WTAP enhanced the abilities of HKFs proliferation, migration, and invasion, but upregulating HOXA5 showed the opposite effect on HKFs. Moreover, HOXA5 could be mediated the m6A modification by WTAP, and HOXA5 overexpression reversed the promotive effect of WTAP overexpression on HKFs by activating p53 pathway. Conclusion WTAP can mediate the m6A modification of HOXA5 to regulate p53 pathway, thereby accelerating keloids formation. Our findings provide new insights into the mechanisms of keloid formation by m6A modification, which may promote the development of targeted therapies for keloids to reduce the recurrence rate.