Construction of a Novel Cuproptosis-Related ceRNA Network-SNHG3/miR-1306-5p/PDHA1 and Identification of SNHG3 as a Prognostic Biomarker in Hepatocellular Carcinoma

Abstract

The crucial role of competitive endogenous RNA (ceRNA) in the malignant biological behavior of tumors has been certificated. Nevertheless, the detailed function and molecular mechanism of ceRNA associated with cuproptosis in hepatocellular carcinoma (HCC) remains dismal. In this study, we first constructed a protein–protein interaction network and identified the module with the highest degree of aggregation degree. DLAT and PDHA1 were screened out of the module after differential expression and survival analysis. Next, we reverse-predicted the upstream miRNA and lncRNA from mRNA (DLAT, PDHA1) and successfully established the ceRNA network-SNHG3/miR-1306-5p/PDHA1. SNHG3 was identified to be an independent prognostic biomarker based on the outcome of univariate and multivariate Cox analyses. Subsequently, we implemented methylation, immune infiltration, and drug sensitivity analysis to investigate the potential biological functions of SNHG3 in HCC. In addition, SNHG3 expression was upregulated in liver cancer cell lines. In vitro functional assay revealed that SNHG3 knockdown significantly attenuated proliferation, migration, and invasion of liver cancer cells. In summary, SNHG3 exhibited oncogenic characterization via sponging miR-1306-5p to regulate PDHA1, which might function as a promising prognostic indicator and a potential therapeutic target for HCC and shed new light on the molecular mechanism of HCC progression.