A systematic evaluation of miRNA:mRNA interactions involved in the migration and invasion of breast cancer cells

Abstract

In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the invasiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in invasive cell lines when compared to normal and less invasive cell lines. Transfection of miR-200c, miR-205, and miR-375 mimics into MDA-MB-231 cells led to the inhibition of in vitro cell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, including CFL2, LAMC1, TIMP2, ZEB1, CDH11, PRKCA, PTPRJ, PTPRM, LDHB, and SEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that miR-200c plays a pivotal role in regulating the invasiveness of breast cancer cells. We characterized one of the target genes of miR-200c, CFL2, and demonstrated that CFL2 is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer invasiveness and ultimately lead to the identification of novel biomarkers associated with prognosis.

Prognostic value of miR-141 downregulation in gastric cancer

“…Previous studies have indicated that the expression pattern of miR-141 varies in different malignant tumors. It has been observed that miR-141 was downregulated in pancreatic cancer, renal cancer, hepatocellular carcinoma, and breast cancer, whereas it was upregulated in colorectal cancer and prostate cancer (Yaman Agaoglu et al, 2011;Maruyama et al, 2012;Brunet Vega et al, 2013;Luo et al, 2013;Yu et al, 2013;Yeh et al, 2014). Furthermore, it was also shown that the expression level of miR-141 was associated with cancerspecific survival.…”

Prognostic Significance of Metastasis-Related MicroRNAs in Early Breast Cancer Patients with a Long Follow-up

“…A systematic evaluation of functional miRNA-mRNA interactions associated with the invasiveness of breast cancer cells has revealed that miR-205 was included in a group of 7 downregulated miRNAs in invasive cell lines compared to normal and less invasive cell lines (34 ). It has recently been reported that miR-205 is a tumor suppressor in breast cancer, because breast cancer cell lines express a lower level of miR-205 than nonmalignant cells, and that ectopic expression of miR-205 significantly inhibits cell proliferation and anchorageindependent growth, as well as cell invasion (35 ).…”

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential

“…The ability of tumor cells to invade and destroy neighboring tissues and organs, as well as migrate to other parts of the body, is crucial to the metastatic process [118,119]. It has been increasingly recognized that miRNAs play important roles in tumor invasiveness and metastasis [120][121][122]. For example, Shi et al showed that lower expression of miR-100 could promote the migration and invasion of gastric cancer cells without significant alteration of proliferation [8].…”