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

Abstract

Over two decades of studies on small noncoding RNA molecules illustrate the significance of microRNAs (miRNAs/miRs) in controlling multiple physiological and pathological functions through post-transcriptional and spatiotemporal gene expression. Among the plethora of miRs that are essential during animal embryonic development, in this review, we elaborate the indispensable role of the miR-200 family (comprising miR-200a, -200b, 200c, -141, and -429) in governing the cellular functions associated with epithelial homeostasis, such as epithelial differentiation and neurogenesis. Additionally, in pathological contexts, miR-200 family members are primarily involved in tumor-suppressive roles, including the reversal of the cancer-associated epithelial-mesenchymal transition dedifferentiation process, and are dysregulated during organ fibrosis. Moreover, recent eminent studies have elucidated the crucial roles of miR-200s in the pathophysiology of multiple neurodegenerative diseases and tissue fibrosis. Lastly, we summarize the key studies that have recognized the potential use of miR-200 members as biomarkers for the diagnosis and prognosis of cancers, elaborating the application of these small biomolecules in aiding early cancer detection and intervention.

Keywords: cancer-associated miRNAs; development; epithelial-to-mesenchymal transition (EMT); miR-200 family; miRNA/microRNA; neurodegenerative diseases.

Figure 1

Number of publications per year associated with search terms “miRNA development” and “miRNA disease” in the PubMed database. An increasing trend of publications unearthing miRNAs and their roles during organismal development, as well as during pathological scenarios, clearly denote their vital biological implications.

Figure 2

Classification of the human miR-200 family. Two categories of the human miR-200 family classification exist based on the chromosomal location of the gene (left—gene cluster I and II) and based on seed sequences that bind to 3′ UTR of cognate genes (right—functional group I and II). Illustration created with Biorender.com (https://biorender.com/, accessed on 1 June 2022).

Figure 3

Established and novel functions of the miR-200 family in human cancers. Although certain functions of miR-200s such as EMT suppression are quite well understood, members of the miR-200 family have recently been studied in detail for their novel roles such as RNA editing and reversal of chemoresistance. Illustration created with Biorender.com (https://biorender.com/, accessed on 1 June 2022).