miR-338-3p suppresses colorectal cancer proliferation and progression by inhibiting MACC1.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. This study aimed to elucidate the clinicopathological significance of miR-338-3p and its association with metastasis-associated in colon cancer-1 (MACC1) in CRC. We evaluated miR-338-3p and MACC1 expression in CRC cell lines and analyzed the clinicopathological features of miR-338-3p in 98 samples of CRC tissues. Subsequent Western blot and cellular biological techniques, and xenograft mouse models were performed to investigate the biological role of miR-338-3p and its association with MACC1 in CRC. Our results show that miR-338-3p expression is lower in CRC cell lines and tissues than that in a human normal colonic epithelial cell line and adjacent normal colorectal tissue, respectively. miR-338-3p expression was significantly associated with histological differentiation, UICC stage, T classification, N classification, and M classification in 98 samples of CRC. The overall survival of CRC patients was significantly less in the low miR-338-3p expression group than in the high miR-338-3p expression group (p<0.01). miR-338-3p mimics suppressed cell proliferation, colony formation, migration, and invasion, but induced apoptosis in CRC cells. miR-338-3p inhibitor reversed these biological phenotypes. miR-338-3p mimics or inhibitor suppressed or increased MACC1 expression in HCT116 and SW620. miR-338-3p mimics reversed the effect of increased MACC1 expression induced by HCT116 with MACC1 over-expression plasmid. Increased cell proliferation, colony formation, and suppressed cell apoptosis caused by MACC1 over-expression were significantly reversed in HCT116 transfected with miR-338-3p mimics, respectively. Suppressed cell proliferation, colony formation, migration, invasion, and increased cell apoptosis caused by MACC1 knockdown were significantly reversed in SW620 transfected with miR-338-3p inhibitor, respectively. In vivo, miR-338-3p agomir significantly inhibited xenograft CRC tumor growth and reversed the effect of increased xenograft tumor growth induced from HCT116 with MACC1 overexpression. In conclusion, our data suggest that miR-338-3p suppresses CRC carcinogenesis and progression by inhibiting MACC1. Targeting miR-338-3p might be a novel treatment strategy for CRC. IJCEP