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外泌体miR-608通过靶向BRD4促进食管鳞癌细胞的凋亡
作者:周海浪1  冯亚东2  李桂芹1  黄曙1  周爱军1 
单位:1. 涟水县人民医院 消化内科, 江苏 淮安 223000;
2. 东南大学附属中大医院 消化内科, 江苏 南京 210009
关键词:食管鳞癌 microRNA-608 含溴结构域的蛋白4 凋亡 
分类号:R735.1
出版年·卷·期(页码):2021·49·第八期(862-869)
摘要:

目的:探索外泌体微小RNA-608通过靶向BRD4促进食管鳞癌细胞的凋亡。方法:从涟水县人民医院获得了60例食管鳞状细胞癌(ESCC)和邻近正常组织的患者。采用Norgen Biotek试剂盒提取血清外泌体,通过基因表达微阵列分析患者血清外泌体miRNA表达水平与总生存期(OS)之间的关联;通过生物信息学分析预测miR-608靶标;采用荧光实时定量PCR及蛋白质印迹的方法对miR-608及其靶标蛋白进行含量测定;通过双荧光素酶测定miR-608及其靶标蛋白的结合程度。结果:高水平的miRNA-608表达与更长的OS时间相关(r=-0.874,P<0.05)。转染实验表明,BRD4的上调可能逆转了miRNA-608诱导的凋亡促进作用。结论:miRNA-608通过BRD4的负调控促进ESCC中的凋亡。本研究的结果提供了可改善ESCC患者预后预测的理论基础,也为开发个体化治疗和研究针对这些机制的新疗法提供了机会。

Objective: To explore the exosome miRNA-608 promoting apoptosis of esophageal squamous cell carcinoma cells by targeting BRD4.Methods: 60 patients with esophageal squamous cell carcinoma(ESCC) and adjacent normal tissues were collected from Lianshui County People's Hospital. Serum exosomes were extracted by Norgen Biotek kit, and the association between miRNA expression level of serum exosomes and overall survival(OS) were analyzed by gene expression microarray. Bioinformatics analysis was used to predict miR-608 targets; Fluorescence real-time quantitative PCR and Western blot were used to determine the content of miR-608 and its target proteins. The binding degree of miR-608 and its target protein was determined by dual luciferase.Results: Higher miRNA-608 expression was associated with longer OS time(r=-0.874, P<0.05). Transfection experiments showed that the up-regulation of BRD4 might reverse the promotion of apoptosis induced by miRNA-608. Conclusion: miRNA-608 can promote apoptosis in ESCC through negative regulation of BRD4. The results of this study provide a theoretical basis for predicting improved outcomes in patients with ESCC, as well as an opportunity to develop individualized treatments and to investigate new therapies that target these mechanisms.

参考文献:

[1] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.
[2] LEWIS B P, BURGE C B, BARTEL D P.Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets[J]. Cell, 2005, 120(1):15-20.
[3] BARTEL D P.MicroRNAs:genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2):281-297.
[4] KLOOSTERMAN W P, PLASTERK R H.The diverse functions of microRNAs in animal development and disease[J]. Dev Cell, 2006, 11(4):441-450.
[5] URBICH C, KUEHBACHER A, DIMMELER S.Role of microRNAs in vascular diseases, inflammation, and angiogenesis[J]. Cardiovasc Res, 2008, 79(4):581-588.
[6] SCHICKEL R, BOYERINAS B, PARK S M, et al. MicroRNAs:key players in the immune system, differentiation, tumorigenesis and cell death[J]. Oncogene, 2008, 27(45):5959-5974.
[7] ZHENG D, DING Y, MA Q, et al. Identification of Serum MicroRNAs as novel biomarkers in esophageal squamous cell carcinoma using feature selection algorithms[J]. Front Oncol, 2018, 8:674.
[8] LI D, LIU H, LI Y, et al. Identification of suitable endogenous control genes for quantitative RT-PCR analysis of miRNA in bovine solid tissues[J]. Mol Biol Rep, 2014, 41(10):6475-6480.
[9] SAHRAEI M, CHAUBE B, LIU Y, et al. Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response[J]. J Clin Invest, 2019, 129(12):5518-5536.
[10] JUANG V, CHANG C H, WANG C S, et al. pH-Responsive PEG-shedding and targeting peptide-modified nanoparticles for dual-delivery of irinotecan and microRNA to enhance tumor-specific therapy[J]. Small, 2019, 15(49):e1903296.
[11] BASU A, JIANG X, NEGRINI M, et al. MicroRNA-mediated regulation of pancreatic cancer cell proliferation[J]. Oncol Lett, 2010, 1(3):565-568.
[12] LIANG Z, WANG X, XU X, et al. MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway[J]. Mol Cancer, 2017, 16(1):96.
[13] YANG H, LI Q, NIU J, et al. microRNA-342-5p and miR-608 inhibit colon cancer tumorigenesis by targeting NAA10[J]. Oncotarget, 2016, 7(3):2709-2720.
[14] WANG Z, XUE Y, WANG P, et al. MiR-608 inhibits the migration and invasion of glioma stem cells by targeting macrophage migration inhibitory factor[J]. Oncol Rep, 2016, 35(5):2733-2742.
[15] WANG K, LIANG Q, WEI L, et al. MicroRNA-608 acts as a prognostic marker and inhibits the cell proliferation in hepatocellular carcinoma by macrophage migration inhibitory factor[J]. Tumour Biol, 2016, 37(3):3823-3830.
[16] OTHMAN N, NAGOOR N H.miR-608 regulates apoptosis in human lung adenocarcinoma via regulation of AKT2[J]. Int J Oncol, 2017, 51(6):1757-1764.
[17] FILIPPAKOPOULOS P, QI J, PICAUD S, et al. Selective inhibition of BET bromodomains[J]. Nature, 2010, 468(7327):1067-1073.
[18] DELMORE J E, ISSA G C, LEMIEUX M E, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc[J]. Cell, 2011, 146(6):904-917.
[19] LU T X, ROTHENBERG M E.MicroRNA[J]. J Allergy Clin Immunol, 2018, 141(4):1202-1207.
[20] SEGGERSON K, TANG L, MOSS E G.Two genetic circuits repress the caenorhabditis elegans heterochronic gene lin-28 after translation initiation[J]. Dev Biol, 2002, 243(2):215-225.

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