lncRNA DQ786243 promotes hepatocellular carcinoma cell invasion and proliferation by regulating the miR-15p-5p/Wnt3A axis

Increasing evidence suggests that long noncoding RNAs (lncRNAs) influence the pathogenesis and progression of hepatocellular carcinoma (HCC). The authors of the present study previously reported that abnormal upregulation of lncRNA DQ786243 (lncDQ) was associated with poor prognoses for patients with HCC. However, the elucidation of underlying mechanisms which influenced these results was not completed. Thus, the current study aimed to characterize the mechanisms and functions of lncDQ that facilitate its promotion of HCC progression. lncDQ, miR-15b-5p and Wnt3A expression levels were characterized in HCC and portal vein tumor thrombus tissue samples and for liver cancer and liver cancer cell lines using reverse transcription-quantitative PCR. Bioinformatics software was used for the analysis of interactions between lncDQ and miR-15b-5p, miR-15b-5p and Wnt3A. Luciferase assays confirmed the binding relationships between miR-15b-5p and the 3 ' untranslated region (UTR) of Wnt3A. Using online databases, prognostic values of miR-15b-5p and Wnt3A were also assessed. Proliferation and invasion assays were used to assess liver cancer and HCC cell functions after individually silencing lncDQ and miR-15b-5p expression in the cells. Western blotting was used for the investigation of alterations of the expression of Wnt3A/beta-catenin and epithelial-mesenchymal transition (EMT) signal pathways. lncDQ and Wnt3A expression were significantly increased in HCC tissues, whereas miR-15b-5p was downregulated in HCC tissues. Low expression of miR-15b-5p was also associated with poor prognoses for patients with HCC. lncDQ was able to bind with miR-15b-5p and served as a competing endogenous RNA. As the target gene of miR-15b-5p, Wnt3A was correlated with poor prognoses for patients with HCC. Silencing of lncDQ expression significantly attenuated proliferation and invasion of liver cancer and HCC cells, however the inhibition of miR-15b-5p was able to reverse this effect. However, silencing of lncDQ and miR-15b-5p expression simultaneously resulted in the partial rescue of the inhibitory effect in the liver cancer and HCC cells. lncDQ inhibited miR-15b-5p so as to promote HCC cell invasion and proliferation through activation of the Wnt3A/beta-catenin/EMT pathway. Taken together, the results of the present study suggested that the lncDQ/miR-15b-5p axis modulates the progression of HCC.

Automated summary

The study reveals that lncRNA DQ786243 (lncDQ) plays a role in promoting hepatocellular carcinoma (HCC) progression by modulating the expression of miR-15b-5p and Wnt3A. Low levels of miR-15b-5p are associated with poor prognoses for HCC patients, while silencing lncDQ can attenuate proliferation and invasion of liver cancer and HCC cells.