A Family of Pleiotropically Acting MicroRNAs in Cancer Progression, miR-200: Potential Cancer Therapeutic Targets

Hai-Feng      Zhang; Li-Yan      Xu; En-Min      Li

doi:10.2174/13816128113199990519

Abstract

Recently, a group of microRNAs (miRNAs), the miR-200 family (miR-200s) has been found to be deregulated in multiple types of cancers, in which this family of miRNAs was demonstrated to play a pivotal role in tumor initiation, maintenance, malignant metastasis and chemotherapy resistance. By targeting several central inducers of the epithelial-to-mesenchymal transition (EMT), e.g. ZEB1, ZEB2 and SLUG, miR-200s are currently recognized as master regulators of EMT, thereby suppressing cancer invasion and metastasis. The involvement of miR-200s in angiogenesis has also been reported, and they were found to directly target VEGF-A, FLT1/VEGFR1 and KDR/VEGFR2, three key components of the VEGF signaling pathway. Importantly, miR-200s also modulate the self-renewal ability of cancer stem cells by targeting BMI1 and SUZ12. Aberrant expression of miR-200s has been shown to confer chemoresistant properties to various kinds of cancers. Thus, miR-200s, by playing critical and pleiotropic roles in malignancies, are promising targets for cancer therapy. Notably, it has been shown that several types of natural agents and herbal extracts could be employed to manipulate the expression of miR-200s, making the targeting of miR-200s in cancer therapy more clinically attractive. Nevertheless, a very recent study reported a metastasis-promoting role of miR-200s in breast cancer; thus, careful assessment should be conducted before applying therapeutic interventions using miR-200s as treatment targets. In this review, we will focus on our emerging understanding of the roles of miR- 200s in cancer, specifically their therapeutic potential in treating cancer.

Keywords: miR-200 family, epithelial-to-mesenchymal transition, tumor metastasis, cancer stem cells, angiogenesis, cancer therapeutics.

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