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FRZB is Regulated by the Transcription Factor EGR1 and Inhibits the Growth and Invasion of Triple-Negative Breast Cancer Cells by Regulating the JAK/STAT3 Pathway

  • Haixia Liu
    Correspondence
    Department of Pathology, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China
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  • Yu Mei
    Correspondence
    Department of Breast Surgery, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China
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  • Xiaoshan Ma
    Correspondence
    Community health Service Center of Ganshiqiao, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China
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  • Xiaoyan Zhang
    Correspondence
    Department of Pharmacy, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China
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  • Wenying Nie
    Correspondence
    Address for correspondence: Wenying Nie, Department of Children's Health Care, Jinan Maternity and child care Hospital Affiliated to Shandong First Medical University, No.2, Jianguo Xiaojingsan street, Jinan, 250001, Shandong, P.R. ChinaDepartment of Children's Health Care, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shangdong, P.R. China
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      Abstract

      Background

      To explore the expression of frizzled related protein (FRZB) in triple-negative breast cancer (TNBC) and role of FRZB in TNBC cell growth and invasion.

      Methods

      Breast cancer clinical data were downloaded from the Cancer Genome Atlas. FRZB and early growth response 1 (EGR1) mRNA levels in TNBC were measured by quantitative real-time polymerase chain reaction. FRZB protein level was measured by immunohistochemistry and western blot. Proliferation, migration, and invasion of TNBC cells were detected by colony formation, wound healing, and transwell assay, respectively. The protein levels of EGR1, E-cadherin, N-cadherin, Snail, p-JAK1/JAK1, p-JAK2/JAK2, and p-STAT3/STAT3 were measured by western blot. JASPAR was used to predict the binding site of FRZB and EGR1. The binding ability of FRZB and EGR1 was verified by dual-luciferase reporter gene assay and chromatin immunoprecipitation assay.

      Results

      FRZB was low expressed in TNBC tissues and cells. Silencing FRZB promoted cell proliferation, migration, invasion, and EMT and activated JAK/STAT pathway in MDA-MB-468 and MDA-MB-231 cells, but overexpression of FRZB acted opposite effects in MDA-MB-468 and MDA-MB-231 cells. EGR1 was low expressed in TNBC samples and positively correlated with FRZB. Moreover, EGR1 could recover the promotion of silencing FRZB on cell proliferation, migration, invasion, and JAK/STAT pathway in MDA-MB-468 cells, but silencing EGR1 led to the opposite results in MDA-MB-231 cells.

      Conclusion

      FRZB was low expressed in TNBC and was regulated by EGR1, and FRZB inhibited TNBC cell growth and invasion by regulating the JAK/STAT3 pathway.

      Keywords

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