[1]熊焰,梁承蓉*,邵安娜.RIPK 4通过调控NFКB参与TNFα信号通路从而促进卵巢癌细胞增殖和迁移[J].中国计划生育和妇产科,2020,(8):62-66,70.
 XIONG Yan,LIANG Chengrong*,SHAO Anna.RIPK 4 participates in TNFα signaling pathway by regulating NFКB to promote ovarian cancer cell proliferation and migration[J].Chinese Journal of Family Planning & Gynecotokology,2020,(8):62-66,70.
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RIPK 4通过调控NFКB参与TNFα信号通路从而促进卵巢癌细胞增殖和迁移
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《中国计划生育和妇产科》[ISSN:1674-4020/CN:51-1708/R]

卷:
期数:
2020年8期
页码:
62-66,70
栏目:
论著与临床
出版日期:
2020-08-25

文章信息/Info

Title:
RIPK 4 participates in TNFα signaling pathway by regulating NFКB to promote ovarian cancer cell proliferation and migration
作者:
熊焰梁承蓉*邵安娜
荆州市第二人民医院妇产科
Author(s):
XIONG YanLIANG Chengrong*SHAO Anna
Department of Obstetrics and Gynecology,Second People's Hospital of Jingzhou City,Jingzhou Hubei 434000,P.R.China
关键词:
卵巢癌RIPK 4NFКB靶基因分子机制
Keywords:
ovarian cancerRIPK 4NFκB target genesmolecular mechanisms
分类号:
R 73731
摘要:
目的筛选卵巢癌中具有临床意义的潜在药物靶点,研究其在卵巢癌发生发展中的生物学功能和分子机制。方法通过临床数据库GEPIA筛选目的靶基因,分别敲低和过表达目的基因,利用细胞增殖实验和划痕迁移实验验证目的基因在卵巢癌发生发展中的作用;探索目的基因在卵巢癌中发挥功能的潜在分子机制,并通过蛋白免疫印迹实验进行验证。结果共有18个基因在卵巢癌中高表达,且具有显著临床预后相关性;与正常组织相比,受体相互作用蛋白激酶4(receptorinteracting protein kinase 4,RIPK 4)在卵巢癌中显著高表达,且高表达的患者预后不良;敲低RIPK 4显著抑制卵巢癌细胞的生长增殖和迁移,过表达RIPK 4显著促进卵巢癌细胞的生长增殖和迁移;敲低RIPK 4显著减少核因子КB(nuclear factorКgene binding,NFКB)的入核并抑制其下游靶基因的表达;过表达RIPK 4显著增加NFКB的入核并促进其下游靶基因的表达,由此初步证明了RIPK 4可能参与NFКB介导的α肿瘤坏死因子(tumor necrosis factor α,TNFα)信号通路。结论RIPK 4高表达增加NFКB的入核并显著促进其下游靶基因的高表达,从而参与NFКB介导的TNFα信号通路从而促进卵巢癌细胞生长增殖和迁移。
Abstract:
ObjectiveTo screen potential drug targets of clinical significance in ovarian cancer, and study their biological functions and molecular mechanisms in the development of ovarian cancer.MethodsTarget genes were screened by clinical database GEPIA. The target gene was knocked down and overexpressed. Cell proliferation experiments and migration experiments were used to verify the role of the target gene in the development of ovarian cancer. Explored the potential molecular mechanism of the target gene's function in ovarian cancer, and verified it by Western blotting and qPCR.ResultsA total of 18 genes were highly expressed in ovarian cancer and had significant clinical prognostic relevance; compared with normal tissues, RIPK 4 was significantly overexpressed in ovarian cancer, and patients with high expression had a poor prognosis; Knockdown of RIPK 4 significantly inhibited the growth, proliferation and migration of ovarian cancer cells, and overexpression of RIPK 4 significantly promoted the growth, proliferation and migration of ovarian cancer cells; knockdown of RIPK 4 significantly reduced the nucleation of NFκB and inhibited the expression of downstream target genes; overexpression RIPK 4 significantly increased the nuclear entry of NFκB and promoted the expression of its downstream target genes, thus preliminarily proving that RIPK 4 may participate in the NFκBmediated TNFα signaling pathway.ConclusionThe high expression of RIPK 4 increases the nuclear entry of NFκB and significantly promotes the high expression of its downstream target genes, thereby participating in the NFκBmediated TNFα signaling pathway and promoting the growth, proliferation and migration of ovarian cancer cells.

参考文献/References:

[1] Eddie Fernando Candido Murta, Millena Prata Jammal, Ana Carolinne da Silva,et al. The role of stroma in ovarian cancer [J]. Immunological Investigations, 2019,36(1):114. [2]Rohlfs Elizabeth M, Learning William G, Friedman Kenneth J,et al. Direct detection of mutations in the breast and ovarian cancer susceptibility gene BRCA1 by PCRmediated sitedirected mutagenesis [J]. Clinical Chemistry, 2020,108(1):112. [3]Yuichiro Hatano, Kayoko Hatano, Maho Tamada,et al. A comprehensive review of ovarian serous carcinoma [J]. Advances in Anatomic Pathology, 2019,26(9):329339. [4]Li XC, Wang MY, Yang M,et al. A mutational signature associated with alcohol consumption and prognostically significantly mutated driver genes in esophageal squamous cell carcinoma [J]. Annals of Oncology, 2018, 29(4):938. [5]Holland P M , Willis C R , Kanaly S , et al. RIP4 Is an ankyrin repeatcontaining kinase essential for keratinocyte differentiation [J]. Current Biology, 2002, 12(16):14241428. [6]Adams S , Munz B . RIP4 is a target of multiple signal transduction pathways in keratinocytes: Implications for epidermal differentiation and cutaneous wound repair [J].experimental cell research, 2010, 316(1):126137. [7]Rountree R B , Willis C R , Dinh H , et al. RIP4 Regulates Epidermal Differentiation and Cutaneous Inflammation [J]. Journal of Investigative Dermatology, 2010, 130(1):102112. [8]Busa T, Jeraiby M, Clémenson A,et al. Confirmation that RIPK4 mutations cause not only BartsocasPapas syndrome but also CHAND syndrome [J]. American Journal of Medical Genetics Part A, 2017, 173(11):3114. [9]Mitchell K, O’Sullivan J, Missero C,et al. Exome sequence identies RIPK4 as the BartsocasPapas syndrome locus [J]. Am J Hum Genet,2012,90,6975. [10]Bin Zhou, WeiChun Guo. Exploration of the inhibiting effect of Notch1 blocker on tumor growth in osteosarcoma mouse models as well as related molecular mechanisms [J]. Journal of Hainan Medical University, 2016, 22(12):354364. [11]Azizmohammadi S , Safari A , Kaghazian M , et al. Highlevel expression of RIPK4 and EZH2 contributes to lymph node metastasis and predicts favorable prognosis in patients with cervical cancer [J]. Oncology Research, 2017, 25(4):495. [12]Kim S W , Oleksyn D W , Rossi R M , et al. Protein kinase Cassociated kinase PKK is required for NFκB signaling and survival in diffuse large Bcell lymphoma cells [J]. Blood, 2008, 111(3):16441653. [13]Meylan, E. RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NFkappaB and is processed during apoptosis [J].Embo Reports, 2002, 3(12):12011208. [14]Tang Z ,Li C , Kang B , et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses [J]. Nucleic Acids Research, 2017,45(1):98102. [15]Gao J , Aksoy B A , Dogrusoz U , et al. Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal [J]. Science Signaling, 2013, 6(269):pl1. [16]Cerami E,Gao J ,Dogrusoz U, et al. The cBio Cancer Genomics Portal: An open platform for exploring multidimensional cancer genomics data [J]. Cancer Discovery, 2012, 2(5):401404. [17]Meunier J,Hayashi T.Sigma1 receptors regulate bcl2 expression by reactive oxygen speciesdependent transcriptional regulation of nuclear factor? [J]. Journal of Pharmacology & Experimental Therapeutics, 2010, 332(2):388397. [18]Essani N A , Fisher M A , Jaeschke H . Inhibition of NFkappa B activation by dimethyl sulfoxide correlates with suppression of TNFalpha formation, reduced ICAM1 gene transcription, and protection against endotoxininduced liver injury [J].Shock, 1997, 7(2):9096. [19]Zambrano S, MllerHackbarth K, Li X,et al. GPRC5b modulates inflammatory response in glomerular diseases via nfκb pathway [J]. Journal of the American Society of Nephrology:JASN, 2019,30(9):15731586. [20]Jennifer P Mitchell, Ruaidhrí J Carmody. NFκB and the transcriptional control of inflammation [J]. International Review of Cell & Molecular Biology, 2018, 335(12):4184. [21]Biswas DK, Shi Q, Baily S, et al. NF‐kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis [J].Proc Natl Acad Sci USA, 2004,101(27):1013710142. [22]Tang X,Liu D,Shishodia S,et al.Nuclear factorkappaB (NFkappaB) is frequently expressed in lung cancer and preneoplastic lesions [J]. Cancer,2006,107(11):26372646. [23]Choi BH, Lee DH, Kim J, et al. Controls of nuclear factorKappa B signaling activity by 5'AMPactivated protein kinase activation with examples in human bladder cancer cells [J]. Int Neurourol J,2016,20(3):182187. [24]Cen H, Zhou M, Leng RX, et al. Genetic interaction between genes involved in NFkappaB signaling pathway in systemic lupus erythematosus [J]. Mol Immunol,2013,56(4):643648. [25]Yang G, Xiao X, Rosen DG, et al. The biphasic role of NFkappaB in progression and chemoresistance of ovarian cancer [J].Clin Cancer Res,2011,17(8):21812194. [26]Xiao X , Yang G , Bai P , et al. Inhibition of nuclear factorkappa B enhances the tumor growth of ovarian cancer cell line derived from a lowgrade papillary serous carcinoma in p53independent pathway [J]. BMC Cancer, 2016, 16(1):113.

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更新日期/Last Update: 2020-08-25