Research Article

RPS24c亚型通过促进MVIH在结直肠癌中的稳定性促进肿瘤血管生成

卷 20, 期 5, 2020

页: [388 - 395] 页: 8

弟呕挨: 10.2174/1566524019666191203123943

价格: $65

摘要

背景:结直肠癌(CRC)是全球第二大死亡原因,远处转移是晚期CRC患者预后不良的原因。 RPS24(核糖体蛋白S24)作为核糖体蛋白,已发现该基因编码不同同工型的多个转录变体。我们以前的研究表明,RPS24在CRC中过表达。但是,尚未完全确定RPS24在肿瘤发生中的作用机理。 方法:采用实时荧光定量PCR或western blotting定量检测CRC组织和细胞株RPS24亚型和lncRNA MVIH的表达。进行内皮管形成测定以确定RPS24对肿瘤血管生成的作用。通过MTT法测定HUVEC的细胞活力,并通过transwell法检测HUVEC的迁移和侵袭能力。用特异性ELISA试剂盒测试了PGK1的分泌。 结果:在这里,我们发现RPS24c亚型是肿瘤血管生成的主要贡献者,这是肿瘤生长和转移的重要过程。实时PCR显示,RPS24c同工型在CRC组织中高表达,而其他同工型在正常和CRC组织中均存在,无统计学差异。而且RPS24蛋白水平的变化主要是由于RPS24c的波动所致。此外,我们观察到,沉默RPS24c可以通过抑制小管形成,HUVEC细胞增殖和迁移来减少血管生成。此外,我们调查了分子机制,并证明RPS24c mRNA与lncRNA MVIH相互作用,结合相互作用增强了彼此的稳定性,从而通过抑制PGK1的分泌而激活了血管生成。 结论:RPS24c通过RPS24c / MVIH / PGK1途径促进CRC中的肿瘤血管生成。 RPS24c抑制可能是CRC中抗血管治疗的新选择。

关键词: RPS24,同工型,结直肠癌,血管生成,MVIH,PGK1。

[1]
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5): E359-86.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[2]
Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin 2014; 64(2): 104-17.
[http://dx.doi.org/10.3322/caac.21220] [PMID: 24639052]
[3]
Fitzmaurice C, Akinyemiju TF, Al Lami FH, et al. Global burden of disease cancer collaboration. global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 Cancer Groups, 1990 to 2016: A systematic analysis for the global burden of disease study. JAMA Oncol 2018; 4(11): 1553-68.
[http://dx.doi.org/10.1001/jamaoncol.2018.2706] [PMID: 29860482]
[4]
Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell 2017; 168(4): 670-91.
[http://dx.doi.org/10.1016/j.cell.2016.11.037] [PMID: 28187288]
[5]
Talmadge JE, Fidler IJ. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res 2010; 70(14): 5649-69.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1040] [PMID: 20610625]
[6]
de la Cruz J, Karbstein K, Woolford JL Jr. Functions of ribosomal proteins in assembly of eukaryotic ribosomes in vivo. Annu Rev Biochem 2015; 84: 93-129.
[http://dx.doi.org/10.1146/annurev-biochem-060614-033917] [PMID: 25706898]
[7]
Zhou X, Liao WJ, Liao JM, Liao P, Lu H. Ribosomal proteins: functions beyond the ribosome. J Mol Cell Biol 2015; 7(2): 92-104.
[http://dx.doi.org/10.1093/jmcb/mjv014] [PMID: 25735597]
[8]
Li C, Ge M, Yin Y, Luo M, Chen D. Silencing expression of ribosomal protein L26 and L29 by RNA interfering inhibits proliferation of human pancreatic cancer PANC-1 cells. Mol Cell Biochem 2012; 370(1-2): 127-39.
[http://dx.doi.org/10.1007/s11010-012-1404-x] [PMID: 22868929]
[9]
Lindström MS, Zhang Y. Ribosomal protein S9 is a novel B23/NPM-binding protein required for normal cell proliferation. J Biol Chem 2008; 283(23): 15568-76.
[http://dx.doi.org/10.1074/jbc.M801151200] [PMID: 18420587]
[10]
Khanna N, Reddy VG, Tuteja N, Singh N. Differential gene expression in apoptosis: identification of ribosomal protein S29 as an apoptotic inducer. Biochem Biophys Res Commun 2000; 277(2): 476-86.
[http://dx.doi.org/10.1006/bbrc.2000.3688] [PMID: 11032747]
[11]
Lohrum MA, Ludwig RL, Kubbutat MH, Hanlon M, Vousden KH. Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 2003; 3(6): 577-87.
[http://dx.doi.org/10.1016/S1535-6108(03)00134-X] [PMID: 12842086]
[12]
Macias E, Jin A, Deisenroth C, et al. An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction. Cancer Cell 2010; 18(3): 231-43.
[http://dx.doi.org/10.1016/j.ccr.2010.08.007] [PMID: 20832751]
[13]
Schneider RK, Schenone M, Ferreira MV, et al. Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9. Nat Med 2016; 22(3): 288-97.
[http://dx.doi.org/10.1038/nm.4047] [PMID: 26878232]
[14]
Xue S, Tian S, Fujii K, Kladwang W, Das R, Barna M. RNA regulons in Hox 5′ UTRs confer ribosome specificity to gene regulation. Nature 2015; 517(7532): 33-8.
[http://dx.doi.org/10.1038/nature14010] [PMID: 25409156]
[15]
Gazda HT, Grabowska A, Merida-Long LB, et al. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet 2006; 79(6): 1110-8.
[http://dx.doi.org/10.1086/510020] [PMID: 17186470]
[16]
Xu WB, Roufa DJ. The gene encoding human ribosomal protein S24 and tissue-specific expression of differentially spliced mRNAs. Gene 1996; 169(2): 257-62.
[http://dx.doi.org/10.1016/0378-1119(96)88652-5] [PMID: 8647458]
[17]
Wang Y, Sui J, Li X, et al. RPS24 knockdown inhibits colorectal cancer cell migration and proliferation in vitro. Gene 2015; 571(2): 286-91.
[http://dx.doi.org/10.1016/j.gene.2015.06.084] [PMID: 26149657]
[18]
Sarcević B. Angiogenesis in malignant tumors. Acta Med Croatica 2001; 55(4-5): 187-90.
[PMID: 12398022]
[19]
Yuan SX, Yang F, Yang Y, et al. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology 2012; 56(6): 2231-41.
[http://dx.doi.org/10.1002/hep.25895] [PMID: 22706893]
[20]
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell 2009; 136(4): 629-41.
[http://dx.doi.org/10.1016/j.cell.2009.02.006] [PMID: 19239885]
[21]
Geisler S, Coller J. RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol 2013; 14(11): 699-712.
[http://dx.doi.org/10.1038/nrm3679] [PMID: 24105322]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy