Abstract
Deregulated miRNAs participate in colorectal carcinogenesis. In this study, miR-218 was found to be downregulated in human colorectal cancer (CRC) by miRNA profile assay. miR-218 was silenced or downregulated in all five colon cancer cells (Caco2, HT29, SW620, HCT116 and LoVo) relative to normal colon tissues. miR-218 expression was significantly lower in 46 CRC tumor tissues compared with their adjacent normal tissues (P < 0.001). Potential target genes of miR-218 were predicted and BMI1 polycomb ring finger oncogene (BMI-1), a polycomb ring finger oncogene, was identified as one of the potential targets. Upregulation of BMI-1 was detected in CRC tumors compared with adjacent normal tissues (P < 0.001) and in all five colon cancer cell lines. Transfection of miR-218 in colon cancer cell lines (HCT116, HT29) significantly reduced luciferase activity of the wild-type construct of BMI-1 3' untranslated region (3'UTR) (P < 0.001), whereas this effect was not seen in the construct with mutant BMI-1 3'UTR, indicating a direct and specific interaction of miR-218 with BMI-1. Ectopic expression of miR-218 in HCT116 and HT29 cells suppressed BMI-1 mRNA and protein expression. In addition, miR-218 suppressed protein expression of BMI-1 downstream targets of cyclin-dependent kinase 4, a cell cycle regulator, while upregulating protein expression of p53. We further revealed that miR-218 induced apoptosis (P < 0.01), inhibited cell proliferation (P < 0.05) and promoted cell cycle arrest in the G2 phase (P < 0.01). In conclusion, miR-218 plays a pivotal role in CRC development through inhibiting cell proliferation and cycle progression and promoting apoptosis by downregulating BMI-1.
Highlights
Colorectal cancer (CRC) is one of the most common malignances and the third leading cause of cancer-related death in the world, with an estimated incidence of 1 million new cases and a mortality of >600,000 deaths annually [1,2]
This result applies to CRC; a subset of miRNAs was found to be aberrantly expressed in CRC, and most of the miRNAs are related to cell proliferation, apoptosis and tumor metastasis [4,8]
We further demonstrated that ectopic expression of miR-218 in colon cancer cells led to reduced cell proliferation and induced apoptosis
Summary
Colorectal cancer (CRC) is one of the most common malignances and the third leading cause of cancer-related death in the world, with an estimated incidence of 1 million new cases and a mortality of >600,000 deaths annually [1,2]. A series of studies have revealed that microRNAs (miRNAs) can regulate the expression of a variety of genes pivotal for tumor development and highlight a novel mechanism participating in CRC pathogenesis [3,4,5]. MiRNAs are reported to play an important role in the pathogenesis of human cancers with disordered genome function [6,7]. This result applies to CRC; a subset of miRNAs was found to be aberrantly expressed in CRC, and most of the miRNAs are related to cell proliferation, apoptosis and tumor metastasis [4,8].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
