MetastamiRs: Non-Coding MicroRNAs Driving Cancer Invasion and Metastasis

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human cancers where they act as oncogenes or tumor suppressors contributing to tumorigenesis. Abnormal miRNA expression may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer. Recently, several miRNAs have been shown to initiate invasion and metastasis by targeting multiple proteins that are major players in these cellular events, thus they have been denominated as metastamiRs. Here, we present a review of the current knowledge of miRNAs in cancer with a special focus on metastamiRs. In addition we discuss their potential use as novel specific markers for cancer progression.

Roles of miR-138 and ISG15 in oral squamous cell carcinoma

“…miRNAs are able to regulate various biological processes, such as metabolism, differentiation, proliferation and apoptosis (4). Numerous studies have demonstrated that miRNAs are able to serve as oncogenes and tumor suppressors, and participate in the development of cancers via regulating tumor cell proliferation, differentiation, apoptosis and other biological processes by degrading mRNA or inhibiting translation of oncogenes or tumor suppressor genes (5,6). miRNAs have been demonstrated to be associated with the development and progression of cancers, and they may have potential applications as biomarkers for the diagnosis of various cancers (7).…”

miR-181b as a key regulator of the oncogenic process and its clinical implications in cancer (Review)

“…Additional studies confirmed a strong association between miRNA and cancer (7)(8)(9)(10)(11). Cancer is characterized by uncontrolled cell growth, high proliferation, anti-apoptosis, acquisition of invasive properties to adjacent tissues and organs and inappropriate cell survival (12)(13)(14). Epigenetic change is crucial in tumorigenesis and miRNAs are key components of epigenetic alterations (15).…”

Functional Roles of microRNAs in Cancer: microRNomes and oncomiRs Connection

“…It seems that these metastamiRs regulate key steps in the metastatic program and processes, such as EMT and angiogenesis. Most commonly, metastamiRs promoting cell migration and invasion have been described [62]. Next, we will review some of the identified microRNAs with a relevant role in metastasis in human cancers.…”

“…However, despite great advancements in the knowledge of metastasis biology, the molecular mechanisms are still not completely understood. Remarkably, a regulatory role for microRNAs in metastasis has been established, thus they have been denominated metastamiRs, as they have pro-and anti-metastatic effects [62]. The term metastamiRs was recently introduced by Welch and colleagues to refer to those regulatory microRNAs which promote or suppress various steps in migration and metastasis of cancer cells [63].…”

“…Because of the availability of robust metastasis models, the vast majority of these metastamirs have been identified in breast and/or mammary tumor cell lines [62]. Ma and coworkers from Robert Weinberg's group evidenced that up-regulation of miR-10b suppressed homeobox D10 (HOXD10) expression, allowing the activation of the prometastatic gene RHOC and initiation of breast cancer invasion and metastasis [73].…”