Regulation of microRNAs in cancer metastasis

Abstract

Metastasis is a phenomenon of crucial importance in defining prognosis in patients with cancer and is often responsible for cancer-related mortality. It is known that several steps are necessary for clonal cells to disseminate from their primary tumor site and colonize distant tissues, thus originating metastatic lesions. Therefore, investigating the molecular actors regulating this process may provide helpful insights in the development of efficient therapeutic responses. Recent evidences have indicated the role of microRNAs (miRNAs) in modulating the metastatic process in solid tumors. miRNAs are small regulatory non-coding RNAs that bind specific target mRNAs, leading to translational repression. miRNAs are known to act as negative regulators of gene expression and are involved in the regulation of biological processes, including cell growth, differentiation and apoptosis, both in physiological conditions and during diseases, such as tumors. In the specific field of tumorigenesis, miRNAs play an important role in mediating oncogenesis and favoring tumor progression, as a result of their ability to modulate epithelial-to-mesenchymal transition (EMT) and other series of events facilitating the formation of metastasis. The role of miRNAs in cancer development has been widely studied and has helped elucidate events such as the change in expression of oncogenes, tumor-suppressors and cancer-related proteins. This review focuses on the mechanisms underlying the role of miRNAs as part of the metastatic process.

miR-429 promotes the proliferation of non-small cell lung cancer cells via targeting DLC-1

“…It has been demonstrated that miRs act as critical regulators in tumorigenesis, and deregulation of specific miRs has been observed in various types of human cancer (4,5). Lang et al (6) reported that the expression of miR-429 was frequently increased in NSCLC compared with normal lung tissues, and it was additionally upregulated in NSCLC cell lines compared with normal lung cells.…”

MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1

“…The findings suggest that miR-126/IRS1 may aid the development of therapeutics to treat EC metastasis. In recent years, the identification of miRs has provided a novel approach for research into the development and progression of various types of human cancer (16). Furthermore, the dysregulation of miRs has been identified to be closely associated with cancer metastasis.…”

Epigenetic regulation by DNA methylation and miRNA molecules in cancer

“…Other studies identified downregulation of, for example, mir-203, miR-212, miR-124, miR-135b and miR-200 family via aberrant promoter hypermethylation that increased metastatic potential of cancer cells through multiple cellular pathways that facilitated epithelial-mesenchymal transition [21].…”