Integrated analysis of ncRNA in hepatocellular carcinoma with CTNNB1 mutations reveals miR-205-5p and miR-3940-3p Axes.

Abstract

Background: Catenin beta 1 (CTNNB1) mutations are one of the most common mutations involved in hepatocellular carcinoma (HCC) progression. However, the association between CTNNB1 mutations and HCC remains controversial.

Methods: Five tumor samples with wild-type CTNNB1 and three tumor samples with CTNNB1 mutations were collected from patients with HCC for whole transcriptome sequencing. Selected ncRNAs and mRNAs were validated by qPCR in 48 HCC tumors. Selected ncRNA regulatory axes were verified in HCC cells by transfecting mimics and inhibitors of miRNA.

Results: A network of differentially expressed (DE) lncRNA/circRNA-miRNA-mRNA was constructed to explore the effects of CTNNB1 mutations on ncRNA regulation. TXNRD1, CES1, MATN2, SERPINA5, lncRNA STAT4-210, hsa_circ_0007824, hsa_circ_0008234, hsa-miR-205-5p and hsa-miR-199a-5p were verified at the RNA expression level to validate the sequencing results. The down-up-down axes GLIS3-209/circ_0085440-miR-205-5p-GHRHR and WNK2-213-miR-3940-3p-LY6E were verified at the expression level, and proved to inhibit and promote cell proliferation, respectively.

Conclusion: This study demonstrated CTNNB1 mutations associated ncRNA regulatory axes playing different roles in HCC cell proliferation, providing novel insights into the controversial role of CTNNB1 in HCC.