Overexpression of miR-301a-3p promotes colorectal cancer cell proliferation and metastasis by targeting deleted in liver cancer-1 and runt-related transcription factor 3.

Colorectal cancer (CRC) is the third most common type of cancer. MicroRNAs have been reported to participate in the progression of various cancers. In previous studies, miR-301a-3p expression was shown to be upregulated in CRC tissues. However, the underlying mechanism of miR-301a-3p in CRC has not yet been elucidated. Herein, the level of miR-301a-3p was found to be significantly upregulated in CRC clinical tissues and cell lines (HT29 and SW620). In addition, overexpression of miR-301a-3p obviously promoted cell proliferation, migration and invasion, and inhibited cell apoptosis in CRC cells. Meanwhile, upregulated miR-301a-3p expression also enhanced the expressions of Bax, caspase-3, caspase-9, matrix metalloproteinase (MMP)-2, and MMP-9, while the expression of Bax-2 was decreased. Furthermore, deleted in liver cancer-1 (DLC-1) and runt-related transcription factor 3 (RUNX3) were verified to be direct target genes of miR-301a-3p. Furthermore, overexpression of DLC-1 and RUNX3 revealed antitumor effects in CRC cell lines with the inhibition of cell proliferation, migration and invasion, and the induction of cell apoptosis. In addition, the expressions of Bax, caspase-3, caspase-3, MMP-2, and MMP-9 could be decreased after upregulating the expressions of DLC-1 and RUNX3, along with the upregulation of Bax-2. Moreover, overexpression of miR-301a-3p could promote the growth of xenograft tumors and liver metastasis in vivo, along with reducing the expressions of DLC-1 and RUNX3. Overall, miR-301a-3p might act as a tumor inducer in CRC cells through negatively regulating DLC-1 and RUNX3.