IGJ suppresses breast cancer growth and metastasis by inhibiting EMT via the NF-& kappa;B signaling pathway

作者全名："Wang, Mengxue; Wu, Yushen; Li, Xunjia; Dai, Meng; Li, Shengwei"

作者地址："[Wang, Mengxue; Li, Shengwei] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Wang, Mengxue; Wu, Yushen] Chongqing Med Univ, Chongqing Key Lab Mol Oncol & Epigenet, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Wu, Yushen] Chongqing Med Univ, Dept Oncol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Li, Xunjia] Chongqing Tradit Chinese Med Hosp, Dept Nephrol, Chongqing 400013, Peoples R China; [Dai, Meng] Chongqing Univ, Dept Geriatr Oncol, Dept Palliat care, Canc Hosp, Chongqing 400030, Peoples R China; [Li, Shengwei] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Li, SW (通讯作者)，Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：INTERNATIONAL JOURNAL OF ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001050501000001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：63

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：IGJ; breast cancer; metastasis; epithelial-to-mesenchymal transition; NF-& kappa;B

摘要："Breast cancer metastasis is the primary cause of mortality of patients with breast cancer. The present study aimed to explore the role and underlying mechanisms of IGJ in the invasion and metastasis of breast cancer. The Cancer Genome Atlas database was utilized to analyze the differential gene expression profiles in patients with breast cancer with or without metastasis; the target gene, joining chain of multi-meric IgA and IgM (JCHAIN, also known as IGJ, as referred to herein), with significant expression and with prognostic value was screened. The expression levels of IGJ in human breast cancer paired tissues and cell lines were detected using reverse transcription-quantitative PCR and western blot analysis. IGJ differential expression was detected in paired human breast cancer tissues using immunohistochemistry. The role of IGJ in breast cancer was verified using CCK-8, invasion and migration assays, and scratch tests in vivo and in vitro. Further exploration of the role and mechanism of IGJ in breast cancer was conducted through Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes analysis, western blot analysis and immunofluorescence experiments. Through the analysis of gene expression profiles, it was found that IGJ was poorly expressed in patients with breast cancer with metastasis compared to patients with non-metastatic breast cancer. The overexpression of IGJ was associated with an improved distant metastasis-free survival and overall survival (OS). COX multivariate regression analysis demonstrated that IGJ was an independent prognostic factor for the OS and relapse-free survival of patients with breast cancer. In comparison to healthy breast cancer adjacent tissues and cell lines, IGJ was poorly expressed in breast cancer tissues and cell lines (P<0.05). Further analyses indicated that the overexpression of IGJ suppressed the proliferation, invasion and metastasis of breast cancer cells in vivo and in vitro by inhibiting the occurrence of epithelial-to-mesenchymal transition (EMT) and suppressing the nuclear translocation of p65. Finally, rescue experiments indicated that IGJ restricted the proliferation and metastasis of breast cancer cells by regulating the NF-?B signaling pathway. On the whole, the present study demonstrates that IGJ suppresses the invasion and metastasis of breast cancer by inhibiting both the occurrence of EMT and the NF-?B signaling pathway. These findings may provide novel biomarkers and potential therapeutic targets for the treatment of metastatic breast cancer."

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