The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Abstract

The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters of hairpin precursors located on human chromosome 1 (miR-200b, miR-200a and miR-429) and chromosome 12 (miR-200c and miR-141). The mature -3p products of the precursors are abundantly expressed in epithelial cells, where they contribute to maintaining the epithelial phenotype by repressing expression of factors that favor the process of epithelial-to-mesenchymal transition (EMT), a key hallmark of oncogenic transformation. Extensive studies of the expression and interactions of these miRNAs with cell signaling pathways indicate that they can exert both tumor suppressor- and pro-metastatic functions, and may serve as biomarkers of epithelial cancers. This review provides a summary of the role of miR-200 family members in EMT, factors that regulate their expression, and important targets for miR-200-mediated repression that are involved in EMT. The second part of the review discusses the potential utility of circulating miR-200 family members as diagnostic/prognostic biomarkers for breast, colorectal, lung, ovarian, prostate and bladder cancers.

miRNAs in Cancer (Review of Literature)

“…Examination of miRNAs for specific fractions can significantly increase both the sensitivity and specificity of selected circulating miRNAs as noninvasive biomarkers [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

“…In other words, the mesenchymal/EMT phenotype can revert to mesenchymal-epithelial transition. The miR-200 family can regulate EMT [ 73 , 74 ]. miR-200b plays a critical role in EMT by interacting with genes involved in EMT, including receptors, signaling, and the cell cycle [ 75 ].…”

Revisiting the miR-200 Family: A Clan of Five Siblings with Essential Roles in Development and Disease

“…The miR-200 family has substantial influence on cancer cell motility and invasive behavior through the direct suppression of EMT and metastasis formation in different tumor types. Consequently, many studies have suggested that the miR-200 family has great potential to be key biomarkers in a variety of diseases, including cancer (recently reviewed in [ 199 ], Table 4 ) and neurodegenerative diseases [ 200 , 201 ]. For instance, a recent meta-analysis study encompassing 24 eligible breast cancer articles and 16,565 subjects showed a significant correlation between high miR-200s expression and the poor overall survival of breast cancer patients, while the downregulation of miR-200s was associated with the poor survival of triple-negative and luminal breast cancer patients [ 202 ].…”