microRNA-1297 Inhibits the Growth and Metastasis of Colorectal Cancer by Suppressing Cyclin D2 Expression

Abstract

microRNAs (miR) can potentially be used for categorizing the various subtypes of colorectal cancer (CRC) and predicting a patient's response to treatment with traditional anti-CRC therapies. We investigated how miR-1297 and its potential target molecule cyclin D2 (CCND2) might affect the progression of CRC. Thirty-two pairs of CRC specimens and corresponding samples of para-tumor tissue were collected and examined for their levels of miR-1297 and CCND2 expression. We also examined miR-1297 and CCND2 expression in cultured SW480 cells. The effects of modulated levels of miR-1297 and CCND2 on cell viability, anchorage-independent growth ability, proliferation, apoptosis, cell cycle distribution, migration, and invasion were detected using specific techniques. The possible regulatory effect of miR-1297 on CCND2 was investigated using dual luciferase assays. Our results showed that miR-1297 expression was downregulated in clinical CRC specimens, and such downregulation was associated with upregulated levels of CCND2 expression. Upregulation of miR-1297 and downregulation of CCND2 reduced the proliferation and metastasis potential of SW480 cells, but did not affect the apoptotic process. In addition, miR-1297 regulated CCND2 function by directly binding to the promoter sequence of the CCND2 gene, which would block CCND2-related signaling at the transcription level. Our findings validate the anti-CRC function of miR-1297 and pro-CRC function of CCND2. Our findings may assist in developing miR-based therapies against CRC.