METTL3 alters AK3 RNA expression in an m6A-dependent manner to affect the proliferation and metastasis of hepatocellular carcinoma

Int J Biol Macromol. 2024 Nov 6;282(Pt 5):137213. doi: 10.1016/j.ijbiomac.2024.137213. Online ahead of print.

Abstract

In recent years, the significance of N6-methyladenosine (m6A) modification in the process of tumorigenesis has garnered substantial attention from researchers in the field. Among the myriad of factors involved, METTL3, which functions as an m6A methyltransferase, has emerged as a critical player in this context. This enzyme has been shown to participate actively in the regulation of RNA stability and expression across a diverse array of tumors. To achieve this, we employed quantitative polymerase chain reaction (qPCR) and Western blot analysis techniques to measure the expression levels of both METTL3 and AK3 in various hepatocellular carcinoma cell lines. We utilized small interfering RNA (siRNA) technology to inhibit the expression of METTL3, subsequently observing the resulting changes in AK3 expression. We analyzed the levels of m6A modification using the MeRIP-Seq method to obtain a comprehensive understanding of the underlying molecular interactions. Through MeRIP-Seq analysis, we discovered that METTL3 directly modulates the stability of AK3, thereby promoting its expression via m6A modification. This finding is pivotal as it underscores the regulatory role that METTL3 plays in AK3 RNA expression, facilitated through the M6A modification pathway.

Keywords: AK3 RNA; Hepatocellular carcinoma; METTL3; Proliferation and transfer; m6a dependence.