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.

GAS5, a FoxO1-actived long noncoding RNA, promotes propofol-induced oral squamous cell carcinoma apoptosis by regulating the miR-1297-GSK3β axis

“…Accumulating studies have revealed that miR-1297 plays an important role in cancer. MiR-1297 was reported to suppress tumourigenesis in most cancers, including lung cancer, colorectal cancer, and prostate cancer [31][32][33]. However, we found that GSK3b is a novel target gene of miR-1297.…”

Characterization of microRNA expression in primary human colon adenocarcinoma cells (SW480) and their lymph node metastatic derivatives (SW620)

“… 25 , 26 miR-1297 inhibits the growth and metastasis of colorectal cancer. 27 miR-141 functions as a tumor suppressor in colorectal cancer SW480 cells, 28 and miR-200c regulates cancer progression, epithelial–mesenchymal transition, and drug resistance. 29 , 30 …”

<p>Mechanism of the Regulatory Effect of Overexpression of circMTO1 on Proliferation and Apoptosis of Hepatoma Cells via miR-9-5p/NOX4 Axis</p>

“…MiRNAs are short non-coding RNAs that can negatively regulate target gene expression by binding to the 3ʹ untranslated region (UTR) of the mRNAs through complementary base pairing, and inducing decay or transcriptional repression. 9 MiRNAs have multiple targets that regulate proliferation, differentiation, apoptosis, protein secretion and viral infection, 10,11 and are therefore attractive therapeutic targets. Several miRNAs involved in the development and progression of liver disease have also been identified that can be potential markers for liver cancer diagnosis, prognosis and pharmacogenomics.…”