title: CARMA3 is overexpressed in colon cancer and regulates NF-κB activity and cyclin D1 expression.
abstract: CARMA3 was recently reported to be overexpressed in cancers and associated with the malignant behavior of cancer cells. However, the expression of CARMA3 and its biological roles in colon cancer have not been reported. In the present study, we analyzed the expression pattern of CARMA3 in colon cancer tissues and found that CARMA3 was overexpressed in 30.8% of colon cancer specimens. There was a significant association between CARMA3 overexpression and TNM stage (p=0.0383), lymph node metastasis (p=0.0091) and Ki67 proliferation index (p=0.0035). Furthermore, knockdown of CARMA3 expression in HT29 and HCT116 cells with high endogenous expression decreased cell proliferation and cell cycle progression while overexpression of CARMA3 in LoVo cell line promoted cell proliferation and facilitated cell cycle transition. Further analysis showed that CARMA3 knockdown downregulated and its overexpression upregulated cyclin D1 expression and phospho-Rb levels. In addition, we found that CARMA3 depletion inhibited p-IκB levels and NF-κB activity and its overexpression increased p-IκB expression and NF-κB activity. NF-κB inhibitor BAY 11-7082 reversed the role of CARMA3 on cyclin D1 upregulation. In conclusion, our study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-κB mediated upregulation of cyclin D1.
authors.affiliation: Department of General Surgery, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Miao
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Zhenning
authors.initials: Z
authors.lastname: Wang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xu
authors.forename: Yongxi
authors.initials: Y
authors.lastname: Song
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wu
authors.forename: Huimian
authors.initials: H
authors.lastname: Xu
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000096:biosynthesis* / Q000235:genetics; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D034741:RNA, Small Interfering; D013450:Sulfones / Q000494:pharmacology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D053468:CARD Signaling Adaptor Proteins; C430880:CARD10 protein, human; D016328:NF-kappa B; D009570:Nitriles; D034741:RNA, Small Interfering; D013450:Sulfones; D019938:Cyclin D1