title: CARMA3 overexpression accelerates cell proliferation and inhibits paclitaxel-induced apoptosis through NF-κB regulation in breast cancer cells.
abstract: CARMA3 was recently reported to be overexpressed in several cancers and associated with malignant behavior of cancer cells. However, the expression pattern and biological roles of CARMA3 in breast cancer have not been reported. In the present study, we found that CARMA3 was overexpressed in 41.9 % of breast cancer specimens. Significant association was observed between CARMA3 overexpression and TNM stage (p = 0.0223), tumor size (p = 0.0227), and ErbB-2 status (p = 0.0049). Furthermore, knockdown of CARMA3 expression in MDA-MB-435 cells with high endogenous expression decreased cell proliferation and sensitized cell to paclitaxel-induced apoptosis, while overexpression of CARMA3 in MDA-MB-231 cell line promoted cell proliferation and inhibited apoptosis. Further analysis showed that CARMA3 depletion downregulated, and its overexpression upregulated cyclin D1, Bcl-2, and p-IκB levels. In conclusion, our study demonstrated that CARMA3 is overexpressed in breast cancers. CARMA3 facilitates proliferation and inhibits apoptosis through nuclear factor-kappaB signaling.
authors.affiliation: Department of Surgical Oncology and General Surgery, First Affiliated Hospital, China Medical University, 155 North Nanjing Street, Heping District, Shenyang City, 110001, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Miao
authors.forename: Zhenning
authors.initials: Z
authors.lastname: Wang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wu
authors.forename: Xingyu
authors.initials: X
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: You
authors.forename: Jiguang
authors.initials: J
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053468:CARD Signaling Adaptor Proteins; C430880:CARD10 protein, human; C530104:CCND1 protein, human; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1; D017239:Paclitaxel