Silencing the epitranscriptomic writer METTL3 in Hepatocellular carcinoma cells: A prospective therapeutic approach

N6-methyladenosine (m6A) is a pervasive post-transcriptional modification and has been considered a hotspot issue in the last decade. METTL3 is the major RNA methyltransferase implicated in m6A modification. Limited studies have addressed the pathologic implications of m6A dysregulation in cancer. Our aim was to target METTL3 in HepG2 cell lines by siRNA (small interfering RNA), and then evaluate the effect of this interference on HepG2 cells viability and proliferative activity. Furthermore, the functional impact of METTL3 knockdown was considered by measuring the relative expression of m6A target genes (TP53, eEF2). In the present study METTL3 was targeted using two different siRNAs. HepG2 viability and proliferative activity were conducted by Trypan blue exclusion test and cell proliferation assay, respectively. We revealed that HepG2 viability and proliferative activity were significantly reduced in transfected cells compared to untransfected ones (p< 0.05). Small interference RNA targeted METTL3 significantly reduced the expression of METTL3 in transfected cells, which resulted in up-regulated TP53 and down-regulated eEF2 expression. So, targeting METTL3 significantly hindered HepG2 viability, proliferative activity, and induced apoptosis. Also, post-transcription METTL3 silencing alleviated the disrupted expression of TP53 and eEF2. Therefore, the inhibition of m6A writer enzyme might be a prospective druggable target for Hepatocellular carcinoma (HCC) therapy.