SSTR5‑AS1 functions as a ceRNA to regulate CA2 by sponging miR‑15b‑5p for the development and prognosis of HBV‑related hepatocellular carcinoma.

Abstract

Long non-coding RNAs (lncRNAs) have been implicated in the development and progression of cancer. However, the mechanisms of lncRNAs in hepatitis B virus (HBV) infection-induced hepatocellular carcinoma (HCC) remain unclear. The study aimed to reveal the roles of lncRNAs for HBV-HCC based on the hypothesis of competing endogenous RNA (ceRNA). The lncRNA (GSE27462), miRNA (GSE76903) and mRNA (GSE121248) expression profiles were collected from the Gene Expression Omnibus database. Differentially expressed lncRNAs (DELs), genes (DEGs) and miRNAs (DEMs) were identified using the LIMMA or EdgeR package, respectively. The ceRNA network was constructed based on interaction pairs between miRNAs and mRNAs/lncRNAs. The functions of DEGs in the ceRNA network were predicted using the DAVID database, which was overlapped with the known HCC pathways of Comparative Toxicogenomics Database (CTD) to construct the HCC-related ceRNA network. The prognosis values [overall survival, (OS); recurrence-free survival (RFS)] of genes were validated using the Cancer Genome Atlas (TCGA) data with Cox regression analysis. The present study screened 38 DELs, 127 DEMs and 721 DEGs. A ceRNA network was constructed among 17 DELs, 12 DEMs and 173 DEGs, including the FAM138B-hsa-miR-30c-CCNE2/RRM2 and SSTR5-AS1-hsa-miR-15b-5p-CA2 ceRNA axes. Function enrichment analysis revealed the genes in the ceRNA network that participated in the p53 signaling pathway [cyclin E2 (CCNE2), ribonucleotide reductase M2 subunit (RRM2)] and nitrogen metabolism [carbonic anhydrase 2 (CA2)], which were also included in the pathways of the CTD. Univariate Cox regression analysis revealed that six RNAs (2 DELs: FAM138B, SSTR5-AS1; 2 DEMs: hsa-miR-149, hsa-miR-7; 2 DEGs: CCNE2, RRM2) were significantly associated with OS; while seven RNAs (1 DEL: LINC00284; 3 DEMs: hsa-miR-7, hsa-miR-15b, hsa-miR-30c-2; and 3 DEGs: RRM2, CCNE2, CA2) were significantly associated with RFS. In conclusion, FAM138B-hsa-miR-30c-CCNE2/RRM2 and the SSTR5-AS1-hsa-miR-15b-5p-CA2 ceRNA axes may be important mechanisms for HBV-related HCC.