LncRNA ZEB1‑AS1 reduces liver cancer cell proliferation by targeting miR‑365a‑3p

Abstract

Liver carcinoma is one of the most common malignancies worldwide. Previous studies have demonstrated that long non-coding RNAs (lncRNAs) are crucial mediators that participate in a wide range of molecular processes associated with carcinogenesis. However, little is known about the specific mechanisms that underlie the majority of lncRNAs. Many studies have indicated that lncRNAs affect microRNA (miRNA or miR) activities via physical base-paired binding, therefore serving as competing endogenous RNAs (ceRNAs) that indirectly regulate the expression of miRNA targets. In the current study, it was revealed that lncRNA zinc-finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) serves as a ceRNA for miR-365a-3p, functioning to positively modulate E2F transcription factor 2 (E2F2) expression in liver cancer cells. Additionally, reverse transcription-quantitative polymerase chain reaction demonstrated that levels of ZEB1-AS1 were abnormally upregulated in liver cancer and this was positively correlated with E2F2 expression. Furthermore, high levels of ZEB1-AS1 exhibited a trend for poor survival in patients with liver cancer. Western blot analysis demonstrated that ZEB1-AS1 silencing could reduce E2F2 expression. EdU staining and flow cytometry analysis indicated that downregulation of ZEB1-AS1 could suppress cell proliferation and decrease the S phase proportion of liver cancer cells, which was effectively reversed by the inhibition of miR-365a-3p. ZEB1-AS1 was also determined to be physically associated with miR-365a-3p, while miR-365a-3p was revealed to target the E2F2 3UTR for degradation or translational repression. The results also demonstrated that ZEB1-AS1 positively regulates E2F2 expression by competitively binding to miR-365a-3p. It was further revealed to enhance liver cancer cell proliferation. Thus, these results indicate that ZEB1-AS1 is required for liver cancer progression in a ceRNA dependent manner. ZEB1-AS1 may therefore be a potential target for liver cancer intervention.