MiR-519d-3p suppresses breast cancer cell growth and motility via targeting LIM domain kinase 1
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Breast cancer is the most common female cancer in women, and its estrogen receptor (ER)-negative subtype (ENBC) and triple-negative subtype (TNBC) have unfavorable prognosis in comparison with ER-positive subtype. MiRNAs are small noncoding RNAs that bind to the 3′-UTR region of targeting mRNAs to regulate gene expression. Mir-519d-3p was found to be associated with breast cancer for its potential role in proliferation and metastasis. To explore its potential role and mechanism of miR-519d-3p in breast carcinogenesis, we determined whether miR-519d-3p regulates breast cancer cell proliferation and motility by performing wound-healing assays and migration–invasion assays. We found that miR-519d-3p significantly inhibits proliferation and motility of ENBC and TNBC cells. Overexpression of miR-519d-3p arrested breast cancer cells in the G0/G1 phase and reduced the expression of CDK4, 6/Cyclin D1, and CDK2/Cyclin E1. It was reported that miR-519d-3p or miR-519d-3p expression was associated with cancer metastasis and clinical staging. Since LIM domain kinase 1 (LIMK1) was highly expressed in breast cancer and a major regulator of breast cancer growth and metastasis, we further demonstrated that LIMK1 is a potential target of miR-519d-3p by dual-luciferase report assay. Mir-519d-3p decreases LIMK1 expression at mRNA and protein levels, and the protein level and phosphorylation of cofilin 1 (CFL1), one of the key downstream targets of LIMK1. Our findings suggest that miR-519d-3p regulates the LIMK1/CFL1 pathway in breast cancer and this new venue could be targeted for future breast cancer therapy.
KeywordsMiR-519d-3p Breast cancer Proliferation Metastasis LIM domain kinase 1 Cofilin 1
This work was supported by the Shanghai Municipal Health Bureau of Shanghai, China through Grant No. 201640097 (to L. Fang), the National Natural Science Foundation of China through Grant No. 82172240 (to L. Fang), Cancer Center Support Grant P30 CA016672 from the United States National Institutes of Health (to The University of Texas MD Anderson Cancer Center), startup funds from MD Anderson Cancer Center (to Q. Shen), and the Duncan Family Institute Seed Funding Research Program (to Q. Shen).
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Conflict of interest
The authors declare that they have no conflict of interest.
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