The Effect of METTL3 on the Proliferation and Differentiation of Cutaneous Squamous Cell Carcinoma
Zhou Renpeng, Wang Chen, Fu Xiujun, Wang Danru, Sheng Lingling, Liang Yimin*
The cutaneous squamous cell carcinoma (cSCC) originates from epithelial stem cells through the dysregulation of self-renewal and differentiation. Recently, methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification emerges as a new frontier of research in several cancers. However, little is known about METTL3 in cSCC. This study is aimed to investigate the role of METTL3 in the tumorigenesis of cSCC. We investigated the effect of METTL3 knock down on the WTAP, METTL3 and METTL14 complex and m6A modification levels in cSCC. And we investigated the cell differentiation, proliferation and self-renewal in cSCC in vitro and in vivo. The results demonstrated that the expression of METTL3 was up-regulated in cSCC cells. METTL3 knock down reduced the METTL14 protein levels and m6A modification levels. METTL3 knock down promoted cSCC cell differentiation and increased the expression of IKKα. Also, METTL3 knock down inhibited the cell proliferation and self-renewal and decreased the expression of self-renewal associated genes. In conclusion, we demonstrated a crucial function for METTL3 in regulating cell differentiation and self-renewal in cSCC. Thus, a novel target for cSCC treatment could have been provided.
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