Ring finger protein 43 gene and its function in digestive system cancer

Abstract

Abstract:Ring finger protein 43 (RNF43) is a ringtype E3 ubiquitin ligase. As a negative regulater of Wnt signaling pathway, RNF43 has an important antitumor effect. The mutation of RNF43 may cause abnormal activation of Wnt signaling pathway, and then promote invasion, metastasis and proliferation of tumor cell. In addition, the act of RNF43 protein in the Wnt signal pathway is expected to be a molecular target in the therapy of cancer. In recent years, with the gradual deepening of related research, the molecular structure of RNF43 protein and its mechanism of action with the Wnt pathwayrelated proteins have been gradually clear. In clinical, RNF43 protein analogs and related vaccine also show the important position in the therapy of cancer.

Key words:Gene expression regulation,Digestive system neoplasms,Gene, tumor suppressor,Ring finger protein 43

Qiu Wangwang, Yang Zhili, Zheng Qi. Ring finger protein 43 gene and its function in digestive system cancer[J]. Journal of International Oncology, 2016, 43(1): 56-59.

References

［1］ Vilella AJ, Severin J, UretaVidal A, et al. EnsemblCompara gene trees: complete, duplicationaware phylogenetic trees in vertebrates［J］. Genome Res, 2009, 19(2): 327-335. DOI:10.1101/gr.073585.107. ［2］ Zebisch M, Xu Y, Krastev C, et al. Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist Rspondin［J］. Nat Commun, 2013, 4(16): 458464. DOI:10.1038/ncomms3787. ［3］ De Lau WB, Snel B, Clevers HC. The Rspondin protein family［J］. Genome Biol, 2012, 13(3): 242. DOI:10.1186/gb-2012-13-3-242. ［4］ Clevers H, Nusse R. Wnt/βCatenin signaling and disease［J］. Cell, 2012, 149(6): 1192-1205. DOI:10.1016/j.cell.2012.05.012. ［5］ Hao HX, Xie Y, Zhang Y, et al. ZNRF3 promotes Wnt receptor turnover in an Rspondinsensitive manner［J］. Nature, 2012, 485(7397): 195200. DOI:10.1038/nature11019. ［6］ Koo BK, Spit M, Jordens I, et al. Tumour suppressor RNF43 is a stemcell E3 ligase that induces endocytosis of Wnt receptors［J］. Nature, 2012, 488(7413): 665-669. DOI:10.1038/nature11308. ［7］ Moffat LL, Robinson RE, Bakoulis AA. The conserved transmembrane RING finger protein PLR1 downregulates Wnt signaling by reducing Frizzled, Ror and Ryk cellsurface levels in Celegans［J］. Development, 2014, 141(3): 617-628. DOI:10.1242/dev.101600. ［8］ Moad H, Pioszak AA. Reconstitution of Rspondin: LGR4: ZNRF3 adult stem cell growth factor signaling complexes with recombinant proteins produced in Escherichia coli［J］. Biochemistry, 2013, 52(41): 72957304. DOI:10.1021/bi401090h. ［9］ Chen PH, Chen XY, Lin ZH, et al. The structural basis of Rspondin recognition by LGR5 and RNF43［J］. Genes Dev, 2013, 27(12): 1345-1350. DOI:10.1101/gad.219915.113. ［10］ Peng WC, de Lau W, Madoori PK, et al. Structures of Wntantagonist ZNRF3 and its complex with Rspondin 1 and implications for signaling［J］. PLoS One, 2013, 8(12): e83110. DOI:10.1371/journal.pone.0083110. ［11］ Xie Y, Zamponi R, Charlat O, et al. Interaction with both ZNRF3 and LGR4 is required for the signalling activity of R-spondin［J］. EMBO Rep, 2013, 14(12): 1120-1126. DOI:10.1038/embor.2013.167. ［12］ Takahashi N, Yamaguchi K, Ikenoue T, et al. Identification of two Wntresponsive elements in the intron of RING finger protein 43 (RNF43) gene［J］. PLoS One, 2014, 9(1): e86582. DOI:10.1371/journal.pone.0086582. ［13］ Krausova M, Korinek V. Wnt signaling in adult intestinal stem cells and cancer［J］. Cell Signal, 2014, 26(3): 570-579. DOI:10.1016/j.cellsig.2013.11.032. ［14］ Shinada K, Tsukiyama T, Sho T, et al. RNF43 interacts with NEDL1 and regulates p53mediated transcription［J］. Biochem Biophys Res Commun, 2011, 404(1): 143-147. DOI:10.1016/j.bbrc.2010.11.082. ［15］ Giannakis M, Hodis E, Jasmine Mu X, et al. RNF43 is frequently mutated in colorectal and endometrial cancers［J］. Nat Genet, 2014, 46(12): 1264-1266. DOI:10.1038/ng.3127. ［16］ Wang K, Yuen ST, Xu J, et al. Wholegenome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer［J］. Nat Genet, 2014, 46(6): 573-582. DOI:10.1038/ng.2983. ［17］ Okuno K, Sugiura F, Hidai JI, et al. Phase Ⅰ clinical trial of a novel peptide vaccine in combination with UFT/LV for metastatic colorectal cancer［J］. Exp Ther Med, 2011, 2(1): 73-79. DOI:10.3892/etm.2010.182. ［18］ Inoue K, Sugiura F, Kogita A, et al. Clinical trial of a sevenpeptide vaccine and tegafururacil/leucovorin as combination therapy for advanced colorectal cancer［J］. Gan To Kagaku Ryoho, 2014, 41(10): 12761279. ［19］ Sugiura F, Inoue K, Kogita A, et al. Treatment outcome of peptide vaccination for advanced colorectal cancer［J］. Gan To Kagaku Ryoho, 2013, 40(12): 1584-1586. ［20］ Matsushita N, Aruga A, Inoue Y, et al. Phase Ⅰ clinical trial of a peptide vaccine combined with tegafururacil plus leucovorin for treatment of advanced or recurrent colorectal cancer［J］. Oncol Rep, 2013, 29(3): 951-959. DOI:10.3892/or.2013.2231. ［21］ Hijikata Y, MurahashiIga M, Okazaki T, et al. Development of novel immune therapies for solid tumors: phase Ⅰ clinical trials in a single institute［J］. Rinsho Ketsueki, 2012, 53(5): 487-492. ［22］ Wu J, Jiao Y, Dal Molin M, et al. Wholeexome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitindependent pathways［J］. Proc Natl Acad Sci USA, 2011, 108(52): 21188-21193. DOI:10.1073/pnas.1118046108. ［23］ Sakamoto H, Kuboki Y, Hatori T, et al. Clinicopathological significance of somatic RNF43 mutation and aberrant expression of ring finger protein 43 in intraductal papillary mucinous neoplasms of the pancreas［J］. Mod Pathol, 2015, 28(2): 261-267. DOI:10.1038/modpathol.2014.98. ［24］ Reid MD, Choi H, Balci S, et al. Serous cystic neoplasms of the pancreas: clinicopathologic and molecular characteristics［J］. Semin Diagn Pathol, 2014, 31(6): 475-483. DOI:10.1053/j.semdp.2014.08.009. ［25］ Gala MK, Mizukami Y, Le LP, et al. Germline mutations in oncogeneinduced senescence pathways are associated with multiple sessile serrated adenomas［J］. Gastroenterology, 2014, 146(2): 520529. DOI:10.1053/j.gastro.2013.10.045. ［26］ Xing C, Zhou W, Ding S, et al. Reversing effect of ring finger protein 43 inhibition on malignant phenotypes of human hepatocellular carcinoma［J］. Mol Cancer Ther, 2013, 12(1): 94-103. DOI:10.1158/1535-7163.MCT-12-0672. ［27］ Ong CK, Subimerb C, Pairojkul CA, et al. Exome sequencing of liver flukeassociated cholangiocarcinoma［J］. Nat Genet, 2012, 44(6): 690-1113. DOI:10.1038/ng.2273. ［28］ Jiang X, Hao HX, Growney JD, et al. Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma［J］. Proc Natl Acad Sci USA, 2013, 110(31): 12649-12654. DOI:10.1073/pnas.1307218110.

[1]	Wu Minhang, Sun Wenzheng, Yu Qingzhuo, Guo Rong, Ye Hui, Du Ying, Qiu Jin, An Huazhang, Cao Lili.RNF43 inhibits PD-L1 expressionviaβ-catenin in melanoma cells and promotes CD8⁺T cell-mediated anti-tumor immune reaction[J]. Journal of International Oncology, 2023, 50(7): 407-412.
[2]	Xu Kai, Wen Gang, Li Rui, Tian Yuan.Research progress on the prognostic value of the ratio of lymphocytes to C-reactive protein in digestive system neoplasms[J]. Journal of International Oncology, 2022, 49(10): 627-629.
[3]	Zhang Jing, Huang Shouguo, Xia Ying.Mechanism study of CeRNA regulatory network mediating malignant tumor phenotype[J]. Journal of International Oncology, 2021, 48(9): 544-548.
[4]	Ju Xinyue, Hu Chunmei, Zhao Yue, Tang Yan.CDX2 and gastrointestinal neoplasms[J]. Journal of International Oncology, 2021, 48(6): 374-376.
[5]	Liu Peipei, Yang Mengxue, Yan Xuebing.Research advances of m⁶A methylation modification in digestive system neoplasms[J]. Journal of International Oncology, 2021, 48(11): 688-692.
[6]	Ma Yingji, Sun Libin, Qiu Wensheng.Mechanism of long non-coding RNA GHET1 in tumors of the digestive system[J]. Journal of International Oncology, 2020, 47(5): 304-307.
[7]	Zhu Zemin, Xie Zhiqin, Sun Yongkang, Tang Caixi.MicroRNA-223 and digestive system tumors[J]. Journal of International Oncology, 2020, 47(2): 112-114.
[8]	Qi Ruili, Wang Huaqing.Research progress of tumor vascular targeting drugs combined with PD-1/PD-L1 antibody in the treatment of digestive system tumors[J]. Journal of International Oncology, 2019, 46(12): 750-754.
[9]	LIU Hou-Jie, WAN Jing-Hai.Molecular mechanism in malignant progression of meningioma[J]. Journal of International Oncology, 2018, 45(8): 494-498.
[10]	Shen Kai, Shao Fang, Feng Tongbao, Qi Chunjian.Role of microRNA-373 in tumor[J]. Journal of International Oncology, 2018, 45(6): 355-357.
[11]	Zhou Shuaiyang, Gong Weijuan, Xiao Weiming.Mechanism of angiopoietinlike protein 4 in digestive system neoplasms[J]. Journal of International Oncology, 2018, 45(6): 371-374.
[12]	ZHENG Pan-Chan, SUN Xiao, WANG Li-Hua.Circular RNA and its application in gynecological carcinoma[J]. Journal of International Oncology, 2018, 45(5): 308-311.
[13]	Shanshan, Zhou Yongning, Guan Quanlin.Long non-conding RNA TUG1 and digestive system cancers[J]. Journal of International Oncology, 2018, 45(11): 688-691.
[14]	Ke Jianbo, Ling Zhiqiang, Shang Jinbiao.Research progress of miR-151-5p in tumor[J]. Journal of International Oncology, 2017, 44(6): 445-.
[15]	Zhang Zijin, Ai Bin.Advances of immune checkpoint blockades in the treatment of digestive cancers[J]. Journal of International Oncology, 2017, 44(1): 63-66.