BMC Cancer (Apr 2024)

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

  • Yingmin Wu,
  • Lian Li,
  • Long Wang,
  • Shenjie Zhang,
  • Zhirui zeng,
  • Jieyu Lu,
  • Zhi Wang,
  • Yewei Zhang,
  • Shilong Zhang,
  • Haiyang Li,
  • Tengxiang Chen

DOI
https://doi.org/10.1186/s12885-024-12235-4
Journal volume & issue
Vol. 24, no. 1
pp. 1 – 19

Abstract

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Abstract 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.

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