Maternal embryonic leucine zipper kinase serves as a potential prognostic marker and leads to sorafenib chemoresistance modified by miR-142-5p in hepatocellular carcinoma

Background Chemotherapy is an important treatment strategy for advanced hepatocellular carcinoma (HCC). Sorafenib is a first-line systemic drug that has been commonly used clinically for patients with advanced HCC. However, the high resistance rate of sorafenib in HCC patients often hinders its long-term efficacy. Therefore, it is vital to reveal the molecular mechanisms of sorafenib resistance in patients with HCC. Methods In current study, we screened out fourteen genes that over-expressed in HCC specimens through integrative bioinformatics analysis. Here, maternal embryonic leucine zipper kinase ( MELK ) was highlighted as one of the most probable molecules. The Database for Annotation Visualization and Integrated Discovery (DAVID) program was utilized for functional pathway enrichment analysis. Real-time PCR (RT-PCR) and western blot were used to examine the expression levels of MELK . CCK-8, transwell, colony formation assays and flow cytometry were used to detect cell proliferation, the cell cycle. The dual luciferase assays were performed to study the targeting relationship between MELK and miR-142-5p. Results MELK expressions were correlated significantly with cell proliferation by regulating cell cycle and DNA replication. High MELK expression in patients with HCC indicated a poor prognosis both the overall and diseases free survival rates. MELK knockdown suppresses cell proliferation, migration and invasion in vitro. miR-142-5p regulates MELK expression through binding to the complementary sequence in the 3′-UTR regions. MELK knockdown enhances sensitivity of sorafenib in HCC sorafenib-resistant (HCC/SR) cells. Conclusions MELK may serve as a potential prognostic marker in HCC and MELK knockdown enhanced sensitivity of HepG2/SR cells to sorafenib treatment. Our findings suggest that MELK /miR-142-5p axis could be a potentially therapeutic target for reversing the sorafenib resistance in HCC treatment.