Long noncoding RNA CASC2 regulates hepatocellular carcinoma cell oncogenesis through miR-362-5p/Nf-κB axis.

The long non-coding RNA segment cancer susceptibility candidate 2 (CASC2) has been shown to suppress tumor growth in a variety of cancers, including hepatocellular carcinoma (HCC). However, the mechanism by which CASC2 exerts control over HCC has yet to be established. In the present study, we first demonstrated that CASC2 is downregulated in human HCC tissues and HCC cell lines as compared to adjacent non-tumor tissues (NTTs) and a liver cell line, respectively. After finding that CASC2 knockdown significantly promotes HCC cells migration and invasion as well as that CASC2 overexpression inhibits cell migration and invasion, we identified the microRNA miR-362-5p as an endogenous target of CASC2. Through the use of wild type and mutant CASC2 binding sites inserted into psiCHECK-2 luciferase reporter plasmids, as well as qRT-PCR, we determined that CASC2 overexpression reduces miR-362-5p expression levels, while inhibiting CASC2 activity increases miR-362-5p expression. Past research has shown that miR-362-5p stimulates the NF-κB pathway, which has been implicated in the survival and proliferation of a variety of cancer cells. We therefore investigated the effects of CASC2 expression on NF-κB pathway activity. Ultimately, we determined that CASC2 regulates HCC cell activity by targeting miR-362-5p and thus inhibiting the NF-κB pathway. The present study not only identifies CASC2 as an important HCC cell regulator, but also suggests its mechanism of action. It therefore provides the basis for designing strategies to target CASC2 activity and thereby inhibit HCC growth and progression.