title: CARMA3 regulates the invasion, migration, and apoptosis of non-small cell lung cancer cells by activating NF-кB and suppressing the P38 MAPK signaling pathway.
abstract: In our previous study, CARMA3 overexpression in lung cancer cells promoted cell proliferation and invasion; however, the mechanism underlying the role of CARMA3 in cancer cell invasion remained unclear. In the present study, knockdown of CARMA3 in A549 and H1299 cells suppressed cell invasion and migration, and downregulated matrix metalloprotease 9 expression at the protein and mRNA levels, as shown by Western blotting and real-time PCR. CARMA3 knockdown increased cell apoptosis, as shown by flow cytometry, increased the mRNA and protein expression levels of Bax and Caspase3, and downregulated Bcl-2 in A549 and H1299 cells. Phosphorylated P38 levels increased and NF-кB activation decreased following knockdown of CARMA3. SB203580, a P38 MAPK inhibitor, activated NF-кB, increased cell migration, and inhibited cell apoptosis after knockdown of CARMA3 compared to knockdown of CARMA3 without SB203580. These findings indicate that CARMA3 may suppress the activation of the P38 MAPK signaling pathway to regulate invasion, migration and apoptosis of lung cancer cells by activating NF-кB (P65) in the nucleus.
authors.affiliation: Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China; Department of Pathology, Center Hospital of Wuhan City, Wuhan, Hubei, China.
authors.forename: Z X
authors.initials: ZX
authors.lastname: Xia
authors.affiliation: Department of Radiology, the First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
authors.forename: Z X
authors.initials: ZX
authors.lastname: Li
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, Shenyang Medical College, Shenyang, Liaoning, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
authors.forename: L M
authors.initials: LM
authors.lastname: Sun
authors.affiliation: Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
authors.forename: Q F
authors.initials: QF
authors.lastname: Zhang
authors.affiliation: Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. Electronic address: xueshanqiu1963@163.com.
authors.forename: X S
authors.initials: XS
authors.lastname: Qiu
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D053468:CARD Signaling Adaptor Proteins; C430880:CARD10 protein, human; D004791:Enzyme Inhibitors; D007093:Imidazoles; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C093642:SB 203580
keywords: Apoptosis; CARMA3; Invasion; Migration; NF-кB; P38 MAPK