Background: Colon cancer (CC) is the most commonly occurring malignant tumor in the world. The current cancer treatment options have been less effective especially in the advanced stages of CC and patients have poor overall survival. Hence, there is an urgent need to explore novel molecular therapeutic targets for CC treatment.
Methods: qRT-PCR was performed to detect the levels of lncRNA LINC01224 (LINC01224), microRNA-485-5p (miR-485-5p), MCL1 in CC tumor tissues or cell lines. Two si-RNAs against LINC01224 were used to silence the level of LINC01224, and CCK-8 assay, colony formation assay, and transwell assay were performed to explore the role of LINC01224 on the proliferation, migration, and invasion of CC cell lines. Kaplan–Meier method was applied for evaluating the association between LINC01224 level and the overall survival of CC patients. Through bioinformatics analysis, we found that LINC01224 sponged miR-485-5p and consequently targeted MCL1. Dual-luciferase reporter assay, RNA pull-down assay, qRT-PCR, and Western blot assay were conducted for verification of the interactions among LINC01224, miR-485-5p, and MCL1. Furthermore, the role of LINC01224/miR-485-5p/MCL1 axis in CC progression was investigated by CCK-8 assay, colony formation assay, and transwell assay.
Results: LINC01224 was highly expressed in CC tumor tissues and CC cell lines, and its expression was associated with the overall survival of CC patients. The LINC01224-siRNAs (si-LINC01224) markedly suppressed the level of LINC01224 in CC cell lines (HT29 and SW480 cells) and consequently significantly suppressed the proliferation, migration, and invasion of the HT29 and SW480 cells. LINC01224 was verified to sponge miR-485-5p and consequently targeted MCL1. MiR-485-5p inhibitor or MCL1 overexpression (MCL1 OE) markedly restored the repressive effect of the si-LINC01224 pool on MCL1 expression level, as well as proliferation, migration, and invasion of HT29 and SW480 cells.
Conclusion: This study identified LINC01224/miR-485-5p/MCL1 axis as a novel molecular therapeutic target involved in CC progression.
Keywords: colon cancer, LINC01224, miR-485-5p, MCL1