Overexpression of Metastasis-Associated in Colon Cancer 1-Antisense RNA 1 (MACC1-AS1) in Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits miR-145-5P and Promotes Chemotherapy Resistance of Colorectal Cancer

Abstract

BMSCs have the potential of multipotent differentiation. This study aimed to investigate the interaction between MACC1-AS1 and miR-145-5P in BMSCs and their effect on chemotherapy resistance in colorectal cancer (CRC). BMSCs extracted from mouse marrow were transfected with MACC1-AS1 mimic, or MACC1-AS1 NC (control group). CRC cells were treated wtih gemcitabine and then co-cultured with BMSCs to measure cell viability and invasiveness by MTT and Transwell assay, along with analysis of the expression of MACC1, miR-145-5P, HGF, C-met, P-gp, and MRP. Successful isolation of BMSCs was confirmed by flow cytometry with positive expression of CD44, CD105, and CD90 (purity > 95%). Functionally, overexpression of MACC1-AS1 in BMSCs increased CRC cell viability and invasion, attenuated the inhibitory effect of gemcitabine (p < 0.05). Up-regulation of MACC1-AS1 (9.23±1.21) as demonstrated by RT-qPCR, resulted in a decline of miR-145-5P expression (4.23±1.22) in CRC cells (p < 0.05). In addition, overexpression of MACC1-AS1 increased the expression of HGF, C-met, and multidrug resistance-associated proteins (P-gp, and MRP). In conclusion, overexpression of MACC1-AS1 in BMSCs inhibits miR-145-5P expression to promote colorectal cancer cell progression possibly via activating HGF/C-met pathway and inducing resistance to chemotherapy.