title: CARMA3 is upregulated in human pancreatic carcinoma, and its depletion inhibits tumor proliferation, migration, and invasion.
abstract: Elevated CARMA3 expression has been reported to be involved in tumor progression of several cancer types. In the present study, we examined the expression pattern of CARMA3 protein and its biological roles in human pancreatic carcinoma. Using immunohistochemistry, we checked CARMA3 protein expression in 95 pancreatic ductal carcinoma specimens. We found that CARMA3 was overexpressed in 34 of 95 (35.8 %) specimens. A significant association was observed between CARMA3 overexpression with histological grade (p=0.0099) and nodal status (p=0.0126). To further explore its biological roles, we knocked down CARMA3 expression in CAPAN2 cell line using small interfering RNA (siRNA). MTT growth assay, wound healing assay, and Transwell assay showed that CARMA3 depletion inhibited cell proliferation, migration, and invasion. We also showed that CARMA3 depletion inhibited EGF-induced nuclear factor-kappaB (NF-κB) activation and its target genes' expression. The effect of CARMA3 depletion on NF-κB signaling was significantly reduced in Bcl10-depleted cells. In conclusion, CARMA3 is overexpressed in pancreatic cancer and regulates malignant cell growth, invasion, and NF-κB signaling, which was dependent on its association with Bcl10.
authors.affiliation: Department of Gastroenterology, China-Japan Friendship Hospital, Chaoyang District, Beijing, 100029, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Du
authors.forename: Liping
authors.initials: L
authors.lastname: Jia
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Long
authors.initials: L
authors.lastname: Fang
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Fan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000328:Adult; D000368:Aged; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins / Q000032:analysis / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; C430880:CARD10 protein, human; D016328:NF-kappa B; D004815:Epidermal Growth Factor