miR-214 promotes apoptosis and sensitizes breast cancer cells to doxorubicin by targeting the RFWD2-p53 cascade.

Jiaxuan Zhang, Beibei Su, Chen Gong, Qingsongg Xi, Tengfei Chao

Biochemical and biophysical research communications 2016 Sep 09

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miR-214 is involved in numerous physiological and pathological processes including tumorigenesis. However, the function of miR-214 in the development and treatment of breast cancer remains elusive. In this study, we report that miR-214 is strikingly down-regulated in breast cancer cell lines and clinical samples, particularly, in the doxorubicin resistant tumor tissues. Remarkably, restoration of miR-214 expression induces apoptosis and sensitizes the MCF7 cells sustaining wild-type p53, but not the p53 null MDA-MB-157 cells, to doxorubicin. Furthermore, we reveal that miR-214 directly down-regulates the expression of RFWD2, also known as COP1, an E3 ligase targeting the tumor suppressor p53 for proteasomal degradation. In addition, RFWD2 protein levels are reversely correlated with miR-214 expression levels in breast cancer tissues. Moreover, ectopic expression of RFWD2 markedly abolishes miR-214-triggered apoptosis of MCF7 cells. In conclusion, miR-214 functions as a tumor suppressor by regulating the RFWD2-p53 cascade, thus delivery of miR-214 analogs could be a potential adjunct therapy in breast cancer harboring wild type p53. Copyright © 2016 Elsevier Inc. All rights reserved.

Citation

Jiaxuan Zhang, Beibei Su, Chen Gong, Qingsongg Xi, Tengfei Chao. miR-214 promotes apoptosis and sensitizes breast cancer cells to doxorubicin by targeting the RFWD2-p53 cascade. Biochemical and biophysical research communications. 2016 Sep 09;478(1):337-342