LINC01234/microRNA-31-5p/MAGEA3 Axis Mediates the Proliferation and Chemoresistance of Hepatocellular Carcinoma Cells

Abstract Hepatocellular carcinoma (HCC) is a prevalent malignancy characterized by aggressiveness and poor prognosis, however, the molecular mechanism remains to be fully identified. Based on the analysis of TCGA database, melanoma-associated antigen A3 (MAGEA3) and long non-coding RNA (lncRNA) LINC01234 were up-regulated in HCC and associated with poor prognosis of HCC. We investigated mechanism how MAGEA3 and LINC01234 influenced HCC cellular functions and cisplatin resistance. MAGEA3 depletion inhibited proliferation, invasion, and cisplatin resistance of HepG2 cells and Huh7 cells in vitro, reduced resistance-associated protein 2 (MRP2), MRP3, and multidrug resistance protein 1 (MDR1) expression and elevated ALB expression. RNA pull-down and RIP assays identified the binding of LINC01234 and MAGEA3 to microRNA-31-5p (miR-31-5p). LINC01234 could restore MAGEA3 expression by binding to miR-31-5p. Furthermore, we delivered plasmids into HepG2 cells and Huh7 cells to alter the expression of LINC01234 and miR-31-5p. When miR-31-5p was downregulated, the proliferation and invasion of HepG2 cells and Huh7 cells were enhanced and the cisplatin-induced apoptosis was inhibited, while LINC01234 knockdown could diminish the effects caused by miR-31-5p depletion. In summary, these data highlight the vital role of MAGEA3/LINC01234/miR-31-5p axis in the HCC progression and chemoresistance of HCC cells.