Identification of the prognostic, diagnostic, and biological significance of the miR-148a-3p/cathepsin A axis in hepatocellular carcinoma

J Biochem Mol Toxicol. 2022 Dec;36(12):e23208. doi: 10.1002/jbt.23208. Epub 2022 Sep 6.

Abstract

A comprehensive analysis of the prognostic, diagnostic, and biological significance of miR-148a-3p and cathepsin A (CTSA) in hepatocellular carcinoma (HCC) was performed using bioinformatics algorithms with The Cancer Genome Atlas (TCGA) data. miR-148a-3p and CTSA gene expression in HCC tissues and nontumor specimens was analyzed using TCGA database with R software. CTSA staining analysis was validated using the Human Protein Atlas database. Prognostic, diagnostic, gene set enrichment, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and immune infiltration analyses were implemented using the TCGA database with R software. Based on TCGA data and our cohort populations, CTSA expression was significantly elevated in HCC tissues compared with nontumor specimens. A significant negative correlation between miR-148a-3p and CTSA was observed in the TCGA data and our cohort population. Mechanistically, CTSA was a direct gene target of miR-148a-3p. Both CTSA and miR-148a-3p could serve as prognostic and diagnostic indicators in HCC. miR-148a-3p expression was significantly and negatively correlated with the StromalScore, ImmuneScore, and ESTIMATEScore in patients with liver cancer. miR-148a-3p mimic-mediated apoptosis and the inhibition of HCC cell growth and migration were counteracted by CTSA overexpression. The miR-148a-3p/CTSA axis was implicated in immune cell infiltration and carcinogenesis of HCC. miR-148a-3p and CTSA might be prospective molecular targets to enhance the potency of immunotherapy in HCC.

Keywords: apoptosis; diagnosis; hepatocellular carcinoma; immune infiltration; immunotherapy; migration; prognosis.

MeSH terms

  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Cathepsin A / genetics
  • Cathepsin A / metabolism
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • MicroRNAs* / metabolism
  • Prognosis

Substances

  • Cathepsin A
  • MicroRNAs
  • CTSA protein, human
  • MIRN148 microRNA, human