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Hepatocellular carcinoma (HCC) is one of the most deadly malignant cancers worldwide. Research into the crucial genes responsible for maintaining the aggressive behaviour of cancer cells is important for the clinical treatment of HCC. The purpose of this study was to determine whether the E3 ubiquitin ligase Ring Finger Protein 125 (RNF125) plays a role in the proliferation and metastasis of HCC. RNF125 expression in human HCC samples and cell lines was investigated using TCGA dataset mining, qRT‒PCR, western blot, and immunohistochemistry assays. In addition, 80 patients with HCC were studied for the clinical value of RNF125. Furthermore, the molecular mechanism by which RNF125 contributes to hepatocellular carcinoma progression was determined with mass spectrometry (MS), coimmunoprecipitation (Co-IP), dual-luciferase reporter assays, and ubiquitin ladder assays. We found that RNF125 was markedly downregulated in HCC tumour tissues, which was associated with a poor prognosis for patients with HCC. Moreover, the overexpression of RNF125 inhibited HCC proliferation and metastasis both in vitro and in vivo, whereas the knockdown of RNF125 exerted antithetical effects. Mechanistically, mass spectrometry analysis revealed a protein interaction between RNF125 and SRSF1, and RNF125 accelerated the proteasome-mediated degradation of SRSF1, which impeded HCC progression by inhibiting the ERK signalling pathway. Furthermore, RNF125 was detected to be the downstream target of miR-103a-3p. In this study, we identified that RNF125 is a tumour suppressor in HCC and inhibits HCC progression by inhibiting the SRSF1/ERK pathway. These findings provide a promising treatment target for HCC.

ABSTRACTN6-Methyladenosine (m6A) plays key roles in the regulation of biological functions and cellular mechanisms for ischaemia reperfusion (IR) injury in different organs. However, little is known about the underlying mechanisms of m6A-modified mRNAs in hepatic IR injury. In mouse models, liver samples were subjected to methylated RNA immunoprecipitation with high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). In total, 16917 m6A peaks associated with 4098 genes were detected in the sham group, whereas 21,557 m6A peaks associated with 5322 genes were detected in the IR group. There were 909 differentially expressed m6A peaks, 863 differentially methylated transcripts and 516 differentially m6A modification genes determined in both groups. The distribution of m6A peaks was especially enriched in the coding sequence and 3‘UTR. Furthermore, we identified a relationship between differentially m6A methylated genes (fold change≥1.5/≤ 0.667, pvalue≤0.05) and differentially expressed genes (fold change≥1.5 and pvalue≤0.05) to obtain three overlapping predicted target genes (Fnip2, Phldb2, and Pcf11). Our study revealed a transcriptome-wide map of m6A mRNAs in hepatic IR injury and might provide a theoretical basis for future research in terms of molecular mechanisms.