m1A regulator-mediated methylation modification patterns correlated with autophagy to predict the prognosis of hepatocellular carcinoma

Background N1-methyladenosine (m.sup.1A), among the most common internal modifications on RNAs, has a crucial role to play in cancer development. The purpose of this study were systematically investigate the modification characteristics of m.sup.1A in hepatocellular carcinoma (HCC) to unveil its potential as an anticancer target and to develop a model related to m.sup.1A modification characteristics with biological functions. This model could predict the prognosis for patients with HCC. Methods An integrated analysis of the TCGA-LIHC database was performed to explore the gene signatures and clinical relevance of 10 m.sup.1A regulators. Furthermore, the biological pathways regulated by m.sup.1A modification patterns were investigated. The risk model was established using the genes that showed differential expression (DEGs) between various m.sup.1A modification patterns and autophagy clusters. These in vitro experiments were subsequently designed to validate the role of m.sup.1A in HCC cell growth and autophagy. Immunohistochemistry was employed to assess m.sup.1A levels and the expression of DEGs from the risk model in HCC tissues and paracancer tissues using tissue microarray. Results The risk model, constructed from five DEGs (CDK5R2, TRIM36, DCAF8L, CYP26B, and PAGE1), exhibited significant prognostic value in predicting survival rates among individuals with HCC. Moreover, HCC tissues showed decreased levels of m.sup.1A compared to paracancer tissues. Furthermore, the low m.sup.1A level group indicated a poorer clinical outcome for patients with HCC. Additionally, m.sup.1A modification may positively influence autophagy regulation, thereby inhibiting HCC cells proliferation under nutrient deficiency conditions. Conclusions The risk model, comprising m.sup.1A regulators correlated with autophagy and constructed from five DEGs, could be instrumental in predicting HCC prognosis. The reduced level of m.sup.1A may represent a potential target for anti-HCC strategies. Keywords: N1-methyladenosine (m.sup.1A), m.sup.1A regulators, Autophagy, Hepatocellular carcinoma (HCC), Prognosis