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

Background: N1-methyladenosine (m¹A), 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 m¹A in hepatocellular carcinoma (HCC) to unveil its potential as an anticancer target and to develop a model related to m¹A 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 m¹A regulators. Furthermore, the biological pathways regulated by m¹A modification patterns were investigated. The risk model was established using the genes that showed differential expression (DEGs) between various m¹A modification patterns and autophagy clusters. These in vitro experiments were subsequently designed to validate the role of m¹A in HCC cell growth and autophagy. Immunohistochemistry was employed to assess m¹A 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 m¹A compared to paracancer tissues. Furthermore, the low m¹A level group indicated a poorer clinical outcome for patients with HCC. Additionally, m¹A modification may positively influence autophagy regulation, thereby inhibiting HCC cells proliferation under nutrient deficiency conditions. Conclusions: The risk model, comprising m¹A regulators correlated with autophagy and constructed from five DEGs, could be instrumental in predicting HCC prognosis. The reduced level of m¹A may represent a potential target for anti-HCC strategies. [ABSTRACT FROM AUTHOR]