LncRNA MIR155HG induces M2 macrophage polarization and drug resistance of colorectal cancer cells by regulating ANXA2

ObjectiveTo investigate the effects of lncRNA MIR155HG and Annexin A2 (ANXA2) on colorectal cancer (CRC) and the mechanism of the MIR155HG/ANXA2 axis.MethodsThe expressions of MIR155HG and ANXA2 in human CRC tissues were analyzed for association with pathological characteristics and prognosis of CRC patients. CRC cell lines (Caco2 and HT29) were used to study the effects of MIR155HG or ANXA2 knockdown on tumor cell behaviors and macrophage polarization as well as the effect of M2 polarization on oxaliplatin resistance of CRC cells. RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter assays were applied to verify the targeting relationships among MIR155HG, miR-650 and ANXA2. Heterotopic xenograft models were established to verify the results of cell experiments.ResultsMIR155HG and ANXA2 were highly expressed in CRC tissues/cells and of prognostic values for CRC patients. Knockdown of MIR155HG or ANXA2 suppressed M2 macrophage polarization, and proliferation, migration, invasion and oxaliplatin resistance of CRC cells. MIR155HG competed with ANXA2 for binding miR-650 and can also directly target ANXA2. Knockdown of MIR155HG or ANXA2 also inhibited M2 macrophage polarization and CRC progression in nude mice.ConclusionThis study highlighted that MIR155HG, by regulating the miR-650/ANXA2 axis, promotes CRC progression and enhances oxaliplatin resistance in CRC cells through M2 macrophage polarization.