Cancer Management and Research (Sep 2020)
Long Noncoding RNA EBLN3P Promotes the Progression of Liver Cancer via Alteration of microRNA-144-3p/DOCK4 Signal
Abstract
Hang Li,1 Min Wang,2 Hui Zhou,3 Shan Lu,3 Bo Zhang4 1Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital, Changchun, People’s Republic of China; 2Department of Pathology, Jilin Provincial Cancer Hospital, Changchun, People’s Republic of China; 3Department of Anesthesiology, China-Japan Union Hospital, Changchun, People’s Republic of China; 4Department of Pediatric Neurology, First Hospital of Jilin University, Changchun, Jilin 130012, People’s Republic of ChinaCorrespondence: Bo ZhangDepartment of Pediatric Neurology, First Hospital of Jilin University, Changchun, Jilin 130012, People’s Republic of ChinaEmail [email protected]: Therapy for patients with liver cancer in the advanced stage remains a great challenge, and there are very few approved treatments. Although accumulated evidence demonstrates the importance of lncRNAs in liver cancer, data on the functional roles and molecular mechanisms of endogenous bornavirus-like nucleoprotein (EBLN3P) have been rarely reported.Materials and Methods: The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P. The regulatory roles of EBLN3P and miR-144-3p in cell proliferation, migration and invasion ability were verified by the Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interactions among EBLN3P, miR-144-3p and DOCK4 were explored by a luciferase assay and Western blotting. The expression of EBLN3P and microRNA (miR)-144-3p in liver cancer tissues was quantified by reverse transcription-quantitative PCR, and the expression of dedicator of cytokinesis 4 (DOCK4) was quantified by immunohistochemical analysis.Results: The present results revealed that overexpression of EBLN3P or knockdown of miR-144-3p promoted liver cancer cell proliferation, migration and invasion. Bioinformatics analysis and a luciferase assay demonstrated that EBLN3P directly interacts with miR-144-3p to attenuate miR-144-3p binding to the 3ʹ-untranslated region of DOCK4. Furthermore, the mechanistic investigations showing that the miR-144-3p/DOCK4 regulatory loop was activated by knockdown of miR‐144-3p or overexpression of DOCK4 validate the roles of EBLN3P in promoting liver cancer cell proliferation, migration and invasion in vitro. Elevated levels of EBLN3P and DOCK4 and decreased miR-144-3p expression were observed in both liver cancer tissues and cell lines.Conclusion: The present study is the first to demonstrate that EBLN3P may act as a ceRNA to modulate DOCK4 expression by competitively sponging miR-144-3p, leading to the regulation of liver cancer progression, which provides new insights for liver cancer diagnosis and treatment.Keywords: competing endogenous RNAs, dedicator of cytokinesis 4, long noncoding RNAs, microRNAs, liver cancer, endogenous bornavirus-like nucleoprotein
