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

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

Conclusions: The risk model, comprising mA regulators correlated with autophagy and constructed from five DEGs, could be instrumental in predicting HCC prognosis. The reduced level of mA may represent a potential target for anti-HCC strategies.