目的探讨miR-24对人结肠癌SW620细胞CARMA3(含半胱天冬酶募集结构域的膜相关乌苷酸激酶蛋白3)的靶向调控作用及对细胞增殖的影响。方法培养SW620细胞,用生物信息学预测miR-24和CARMA3的靶向匹配关系,并用双荧光素酶报告基因系统鉴定。Li...目的探讨miR-24对人结肠癌SW620细胞CARMA3(含半胱天冬酶募集结构域的膜相关乌苷酸激酶蛋白3)的靶向调控作用及对细胞增殖的影响。方法培养SW620细胞,用生物信息学预测miR-24和CARMA3的靶向匹配关系,并用双荧光素酶报告基因系统鉴定。Lipo3000转染miR-24模拟物后,real-time PCR检测miR-24和CARMA3 m RNA表达; Western blot检测CARMA3蛋白表达; CCK8法检测SW620细胞增殖。结果 miR-24和CARMA3匹配良好,miR-24能够结合CARMA3 m RNA 3'UTR,并有效抑制其表达(P <0. 05)。miR-24能够负向调控CARMA3表达和SW620细胞增殖(P<0. 05)。结论 miR-24通过靶向作用于CARMA3 m RNA 3'UTR能够负向调控CARMA3基因的表达及负向调控SW620细胞的增殖。展开更多
BACKGROUND Primary hepatocellular carcinoma (HCC) is a very malignant tumor in the world. CARMA3 plays an oncogenic role in the pathogenesis of various tumors. However, the function of CARMA3 in HCC has not been fully...BACKGROUND Primary hepatocellular carcinoma (HCC) is a very malignant tumor in the world. CARMA3 plays an oncogenic role in the pathogenesis of various tumors. However, the function of CARMA3 in HCC has not been fully clarified. AIM To study the biological function of CAEMA3 in HCC. METHODS Tissue microarray slides including tissues form 100 HCC patients were applied to access the expression of CARMA3 in HCC and its clinical relevance. Knockdown and overexpression of CARMA3 were conducted with plasmid transfection. MTT, colony formation, and apoptosis assays were performed to check the biological activity of cells. RESULTS Higher expression of CARMA3 in HCC was relevant to poor prognostic survival (P < 0.05). Down-regulation of CARMA3 inhibited proliferation and colony formation and induced apoptosis in HCC cell lines, while increasing its expression promoted tumorigenesis. We also found that sodium aescinate (SA), a natural herb extract, exerted anti-proliferation effects in HCC cells by suppressing the CARMA3/nuclear factor kappa-B (NF-κB) pathway. CONCLUSION Overexpression of CARMA3 in HCC tissues correlates with a poor prognosis in HCC patients. CARMA3 acts pro-tumorigenic effects partly through activation of CARMA3/NF-κB. SA inhibits HCC growth by targeting CARMA3/NF-κB.展开更多
G protein-coupled receptors （GPCRs） play pivotal roles in regulating various cellular functions. It has been well established that GPCR activates NF-κB and aberrant regulation of GPCR-NF-κB signaling axis leads to...G protein-coupled receptors （GPCRs） play pivotal roles in regulating various cellular functions. It has been well established that GPCR activates NF-κB and aberrant regulation of GPCR-NF-κB signaling axis leads to cancers. However, how GPCRs induce NF-κB activation remains largely elusive. Recently, it has been shown that a novel scaffold protein, CARMA3, is indispensable in GPCR-induced NF-κB activation. In CARMA3-deficient mouse embryonic fibroblast cells, some GPCR ligand-, like lysophosphatidic acid （LPA）, induced NF-κB activation is completely abolished. Mechanistically, upon GPCR activation, CARMA3 is linked to the membrane by β-arrestin 2 and phosphorylated by some PKC isoform. Phosphorylation of CARMA3 unfolds its steric structure and recruits its downstream effectors, which in turn activate the IKK complex and NF-κB. Interestingly, GPCR （LPA）-CARMA3-NF-κB signaling axis also exists in ovarian cancer cells, and knockdown of CARMA3 results in attenuation of ovarian cancer migration and invasion, suggesting a novel target for cancer therapy. In this review, we summarize the biology of CARMA3, discuss the GPCR （LPA）-CARMA3-NF-κB signaling axis in ovarian cancer and speculate its potential role in other types of cancers. With a strongly increasing tendency to identify more LPA-like ligands, such as endothelin-1 and angiotensin II, which also activate NF-κB through CARMA3 and contribute to myriad diseases, GPCR-CARMA3-NF-κB signaling axis is emerging as a novel drug target for various types of cancer and other myriad diseases.展开更多
Dear Editor,Chemotherapy is one of major means for cancer treatments, and many of chemotherapeutic drugs are DNA damaging agents that reduce tumor growth through triggering cancer cell apoptosis or necrosis. Following...Dear Editor,Chemotherapy is one of major means for cancer treatments, and many of chemotherapeutic drugs are DNA damaging agents that reduce tumor growth through triggering cancer cell apoptosis or necrosis. Following DNA damage, ataxia telangiectasia mutated （ATM）, a protein kinase, was acti- vated and a cytosolic complex containing ATM, NEMO, RIP1 were formed （Biton and Ashkenazi, 2011）.展开更多
文摘目的探讨miR-24对人结肠癌SW620细胞CARMA3(含半胱天冬酶募集结构域的膜相关乌苷酸激酶蛋白3)的靶向调控作用及对细胞增殖的影响。方法培养SW620细胞,用生物信息学预测miR-24和CARMA3的靶向匹配关系,并用双荧光素酶报告基因系统鉴定。Lipo3000转染miR-24模拟物后,real-time PCR检测miR-24和CARMA3 m RNA表达; Western blot检测CARMA3蛋白表达; CCK8法检测SW620细胞增殖。结果 miR-24和CARMA3匹配良好,miR-24能够结合CARMA3 m RNA 3'UTR,并有效抑制其表达(P <0. 05)。miR-24能够负向调控CARMA3表达和SW620细胞增殖(P<0. 05)。结论 miR-24通过靶向作用于CARMA3 m RNA 3'UTR能够负向调控CARMA3基因的表达及负向调控SW620细胞的增殖。
基金Supported by the Nature Science Foundation of High Education Institution of Anhui Province,No.KJ2017A825Anhui Provincial Natural Science Foundation,No.1808085MH270+2 种基金Foundation of the Higher Education Institution of Henan Province,No.16A320007“Huohua Jihua” Foundation of the Second Hospital of Anhui Medical University Science,No.2015hhjh05Anhui Medical University Science Foundation,No.2017xkj033
文摘BACKGROUND Primary hepatocellular carcinoma (HCC) is a very malignant tumor in the world. CARMA3 plays an oncogenic role in the pathogenesis of various tumors. However, the function of CARMA3 in HCC has not been fully clarified. AIM To study the biological function of CAEMA3 in HCC. METHODS Tissue microarray slides including tissues form 100 HCC patients were applied to access the expression of CARMA3 in HCC and its clinical relevance. Knockdown and overexpression of CARMA3 were conducted with plasmid transfection. MTT, colony formation, and apoptosis assays were performed to check the biological activity of cells. RESULTS Higher expression of CARMA3 in HCC was relevant to poor prognostic survival (P < 0.05). Down-regulation of CARMA3 inhibited proliferation and colony formation and induced apoptosis in HCC cell lines, while increasing its expression promoted tumorigenesis. We also found that sodium aescinate (SA), a natural herb extract, exerted anti-proliferation effects in HCC cells by suppressing the CARMA3/nuclear factor kappa-B (NF-κB) pathway. CONCLUSION Overexpression of CARMA3 in HCC tissues correlates with a poor prognosis in HCC patients. CARMA3 acts pro-tumorigenic effects partly through activation of CARMA3/NF-κB. SA inhibits HCC growth by targeting CARMA3/NF-κB.
文摘G protein-coupled receptors （GPCRs） play pivotal roles in regulating various cellular functions. It has been well established that GPCR activates NF-κB and aberrant regulation of GPCR-NF-κB signaling axis leads to cancers. However, how GPCRs induce NF-κB activation remains largely elusive. Recently, it has been shown that a novel scaffold protein, CARMA3, is indispensable in GPCR-induced NF-κB activation. In CARMA3-deficient mouse embryonic fibroblast cells, some GPCR ligand-, like lysophosphatidic acid （LPA）, induced NF-κB activation is completely abolished. Mechanistically, upon GPCR activation, CARMA3 is linked to the membrane by β-arrestin 2 and phosphorylated by some PKC isoform. Phosphorylation of CARMA3 unfolds its steric structure and recruits its downstream effectors, which in turn activate the IKK complex and NF-κB. Interestingly, GPCR （LPA）-CARMA3-NF-κB signaling axis also exists in ovarian cancer cells, and knockdown of CARMA3 results in attenuation of ovarian cancer migration and invasion, suggesting a novel target for cancer therapy. In this review, we summarize the biology of CARMA3, discuss the GPCR （LPA）-CARMA3-NF-κB signaling axis in ovarian cancer and speculate its potential role in other types of cancers. With a strongly increasing tendency to identify more LPA-like ligands, such as endothelin-1 and angiotensin II, which also activate NF-κB through CARMA3 and contribute to myriad diseases, GPCR-CARMA3-NF-κB signaling axis is emerging as a novel drug target for various types of cancer and other myriad diseases.
文摘Dear Editor,Chemotherapy is one of major means for cancer treatments, and many of chemotherapeutic drugs are DNA damaging agents that reduce tumor growth through triggering cancer cell apoptosis or necrosis. Following DNA damage, ataxia telangiectasia mutated （ATM）, a protein kinase, was acti- vated and a cytosolic complex containing ATM, NEMO, RIP1 were formed （Biton and Ashkenazi, 2011）.
