The miR-200 Family: Versatile Players in Epithelial Ovarian Cancer

Abstract

The role of microRNAs (miRNAs or miRs) in the pathology of epithelial ovarian cancer (EOC) has been extensively studied. Many miRNAs differentially expressed in EOC as compared to normal controls have been identified, prompting further inquiry into their role in the disease. miRNAs belonging to the miR-200 family have repeatedly surfaced over multiple profiling studies. In this review, we attempt to consolidate the data from different studies and highlight mechanisms by which these miRNAs influence progression of metastasis and chemo-resistance in EOC.

Keywords: chemoresistance; expression; metastasis; miR-200 family; ovarian carcinoma.

Figure 1

miRNA-200 family arises from two gene clusters: miR-200b, miR-200a and miR-429 from chromosome 1 (1p33.36) while miR-200c and miR-141 from chromosome 2 (12p13.31). The highlight indicates that in the seed sequence (nucleotides 2–8) the difference is only in one nucleotide.

Figure 2

Model for the expression and mechanisms of action of miR-200 adapted from Bendoraite et al. [49], Mateescu et al. [93] and Prislei et al. [91]. miR-200 could regulate tumorigenic and metastatic transformation by Mesothelial to Epithelial Transition (MET) and Epithelial to Mesenchymal Transition (EMT) respectively. miR-200 expression aided by ROS represses p38α and increases sensitivity to paclitaxel. In cancer cells with low miR-200 expression, this process is not active leading to paclitaxel resistance. Another mechanism involved is the miR-200 mediated down-regulation of TUBB3 in cells with nuclear HuR leading to better clinical response and treatment outcomes.