Characterization of a colorectal cancer migration and autophagy-related microRNA miR-338-5p and its target gene PIK3C3

Colorectal cancer (CRC) has a high metastasis rate. MicroRNA (miRNA) is an epigenetic factor required to regulate cell proliferation, tumor cell growth, cancer formation, and metastasis by regulating tumor-suppressor genes or oncogenes. The objective of this study is to identify miRNAs and their target genes related to CRC migration and metastasis. Previously, we used miRNA microarray to reveal that miR-338-5p was significantly upregulated in patients with recurrent CRC. The expression level of miR-338-5p in tumor tissues of metastatic patients is higher than that in nonmetastatic patients. In this study, we report that miR-338-5p expression level was positively correlated with high migration activity of CRC cells. Overexpression of miR-338-5p induced the migration of CRC HCT-116 cells. Furthermore, overexpression of miR-338-5p inhibited its target gene phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) messenger RNA (mRNA) and protein expression in HCT-116 cells. Downregulation of miR-338-5p increased PIK3C3 mRNA and protein expression in CRC SW480 cells. Furthermore, our study results show that miR-338-5p blocked autophagy, as demonstrated by decreased LC3 type II expression. Autophagy inhibited the migration of colon cancer cell HCT-116 after rapamycin treatment. It can thus be concluded that miR-338-5p induces CRC cell migration by suppressing PIK3C3 expression and autophagy.