Infection with viral hepatitis remains a significant risk factor for hepatocellular carcinoma (HCC). To understand the long noncoding RNAs (lncRNAs) expression and gender differences in HCC, we measured differentially expressed lncRNAs and mRNAs, aiming to provide new possible diagnosis and prognostic candidates for HCC.

Material and methods:
In our study, we performed lncRNA sequencing to analyze the transcriptome profiles of the human HCC-derived HepG2.2.15 cell line treated with estradiol (E2), testosterone, or untreated. Datasets were analyzed by Coding-Non-Coding Index (CNCI), Coding Potential Calculator (CPC), and other software based on lncRNA levels, such as GO term enrichment analysis and KEGG pathway analysis.

We identified 1203 lncRNAs and 29565 mRNAs that were expressed differentially. A total of 269 lncRNAs and 9429 mRNAs obtained from HepG2.2.15 cells treated with E2 were upregulated, and 552 lncRNAs and 7196 mRNAs were downregulated compared to the control group. A total of 163 lncRNAs and 7185 mRNAs were upregulated and 219 lncRNAs and 5755 mRNAs were decreased in the testosterone group compared to the untreated group. GO analysis demonstrated that the differentially expressed genes were involved in biological processes, such as cellular processes, cell components, and binding. KEGG functional pathway analysis revealed that the top 20 enriched pathways of antisense target genes included dopaminergic synapse, GnRH signaling pathway, FoxO signaling pathway, and MAPK signaling pathway.

These differentially expressed genes can provide novel insight into the development of more efficient diagnosis and therapeutic strategies for HCC.