RNA-binding protein CELF2 inhibits breast cancer cell invasion and angiogenesis by downregulating NFATc1

Abstract

Breast cancer constitutes a major cause of morbidity and mortality among women in China and worldwide. The aim of the present study was to investigate whether CUGBP Elav-like family member 2 (CELF2) could inhibit breast cancer cell invasion and angiogenesis by downregulating nuclear factor of activated T cells 1 (NFATc1) expression. The expression of CELF2 and NFATc1 in breast cancer cells and tissues was detected by reverse transcription-quantitative PCR analysis. H&E staining was used to assess the number of microvessels in tumor tissue. The expression of proteins associated with invasion and angiogenesis and NFATc1 in tumor tissues and transfected cells was examined by western blotting. RNA pull-down assay was used to verify the interaction between CELF2 and NFATc1. Cell proliferation, invasion and tube-forming ability was analyzed using Cell Counting Kit-8, Transwell and HUVEC tube formation assays, respectively. CELF2 expression was found to be decreased in breast cancer cells, whereas CELF2 overexpression suppressed the proliferation and invasion of breast cancer cells and inhibited tumor growth and angiogenesis. Furthermore, CELF2 overexpression decreased the expression of N-cadherin (N-cad), CD34 and NFATc1 in tumor tissues, whereas NEAFc1 overexpression increased the expression of N-cad and NFATc1 in MCF cells transfected with OverExp-CELF2. CELF2 was found to be inversely associated with NFATc1, and NFATc1 overexpression reversed the effects of CELF2 overexpression. In conclusion, the findings of the present study demonstrated that CELF2 may inhibit breast cancer cell invasion and angiogenesis by downregulating NFATc1.