Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 63, Issue 3, Pages -Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2023.5553
Keywords
IGJ; breast cancer; metastasis; epithelial-to-mesenchymal transition; NF-& kappa;B
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This study found that IGJ was poorly expressed in breast cancer patients with metastasis. Overexpression of IGJ was associated with improved distant metastasis-free survival and overall survival. Experiment results showed that IGJ inhibited the invasion and metastasis of breast cancer by suppressing epithelial-to-mesenchymal transition (EMT) and the NF-κB signaling pathway.
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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