miR-365通过靶向E2F2抑制胃癌细胞增生和肿瘤形成

doi:10.3969/j.issn.1006-7795.2016.01.001

首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (1): 1-5.doi: 10.3969/j.issn.1006-7795.2016.01.001

• 消化系统重大疾病的全链条研究 • 上一篇下一篇

miR-365通过靶向E2F2抑制胃癌细胞增生和肿瘤形成

郭水龙, 朱圣韬, 程芮, 邵琳琳, 孙秀梅, 张澍田

首都医科大学附属北京友谊医院消化内科国家消化系统疾病临床医学研究中心首都医科大学消化病学系消化疾病癌前病变北京市重点实验室, 北京 100050

收稿日期:2015-12-25 出版日期:2016-02-21 发布日期:2016-02-01
通讯作者: 张澍田 E-mail:zhangshutian@ccmu.edu.cn
基金资助:
国家自然科学基金(81302160, 81272447),国家消化系统疾病临床医学研究中心基金(2015BAI13B09),北京市自然科学基金(7152043)。

miR-365 inhibited the proliferation and tumorigenicity of gastric cancer cells by targeting E2F2

Guo Shuilong, Zhu Shengtao, Cheng Rui, Shao Linlin, Sun Xiumei, Zhang Shutian

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University;National Clinical Research Center for Digestive Diseases;Faculty of Gastroenterology of Capital Medical University;Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing 100050, China

Received:2015-12-25 Online:2016-02-21 Published:2016-02-01
Supported by:
This study was supported by National Natural Science Foundation of China (81302160, 81272447), National Clinical Research Center for Digestive Diseases (2015BAI13B09), Natural Science Foundation of Beijing (7152043).

摘要/Abstract

摘要： 目的研究胃癌相关miR-365调控胃癌细胞增生和肿瘤发生的功能,并通过验证下游靶分子E2F2研究miR-365的作用机制。方法采用Northern blotting法检测miR-365在小鼠各组织器官中的表达谱;real-time PCR检测miR-365在人胃癌组织中的表达变化;细胞实验和裸鼠成瘤实验研究miR-365过表达对胃癌细胞增生的抑制作用;生物信息学分析miR-365下游靶分子E2F2;构建E2F2 3'UTR 野生型和突变型荧光素酶报告载体,并利用双荧光素酶活性分析检测miR-365对E2F2基因表达的调控和结合位点;Western blotting法检测miR-365对E2F2蛋白表达的调控作用。结果 miR-365在包括胃在内的多种消化道组织中表达; miR-365在人胃癌组织中表达显著下调;miR-365过表达显著抑制多种胃癌细胞的增生和裸鼠皮下的成瘤能力;E2F2是miR-365的靶分子,miR-365通过E2F2 3'UTR上的结合位点抑制E2F2的蛋白表达。结论 miR-365 在人胃癌组织和小鼠胃癌模型中表达下调,并通过下游靶分子E2F2抑制胃癌细胞增生和肿瘤形成。

关键词: E2F2, miR-365, 胃癌, microRNA

Abstract: Objective To investigate the regulatory role of miR-365 on proliferation and tumorigenicity of gastric cancer cells, and explore the functional mechanism of miR-365 by verifying its target molecule E2F2 protein. Methods The expression profile of miR-365 in mouse tissues was checked by Northern blotting. The expression of miR-365 in human gastric cancer tissues was detected by Real-Time PCR. The regulatory role of miR-365 on gastric cancer cell proliferation and tumorigenicity were explored with cells experiment and nude mouse tumorigenicity assay; The potential binding site of miR-365 in the E2F2 3' untranslated region (3'UTR) was predicted with the bioinformatic tools; The luciferase report plasmids containing the wild type and mutated binding site of E2F2 3'UTR were constructed, and were used to study the regulation mechanism and identify the binding sites of miR-365 by luciferase activity analysis; The regulation effect of miR-365 on E2F2 protein expression was checked by Western blotting. Results The specific expression of miR-365 was detected in various digestive tissues including stomach; miR-365 was down-regulated in human gastric cancer tissues; miR-365 inhibited the expression of E2F2 protein by recognizing the specific binding site on the 3'UTR of E2F2 mRNA. Conclusion miR-365 was down-regulated in gastric cancer tissues of human and mouse model, and suppressed the proliferation and tumorigenicity of gastric cancer cells by inhibiting the expression of E2F2.

Key words: E2F2, miR-365, gastric cancer, microRNA

中图分类号:

R735.2

郭水龙, 朱圣韬, 程芮, 邵琳琳, 孙秀梅, 张澍田. miR-365通过靶向E2F2抑制胃癌细胞增生和肿瘤形成[J]. 首都医科大学学报, 2016, 37(1): 1-5.

Guo Shuilong, Zhu Shengtao, Cheng Rui, Shao Linlin, Sun Xiumei, Zhang Shutian. miR-365 inhibited the proliferation and tumorigenicity of gastric cancer cells by targeting E2F2[J]. Journal of Capital Medical University, 2016, 37(1): 1-5.

参考文献

[1] Kamangar F, Dores G M, Anderson W F. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world[J]. J Clin Oncol, 2006, 24(14): 2137-2150.
[2] Yang L. Incidence and mortality of gastric cancer in China[J]. World J Gastroenterol, 2006, 12(1): 17-20.
[3] Guo S L, Ye H, Teng Y, et al. Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency[J]. Nat Commun, 2013, 4: 2544.
[4] Zhou X, Xu X, Wang J, et al. Identifying miRNA/mRNA negative regulation pairs in colorectal cancer[J]. Sci Rep, 2015, 5: 12995.
[5] Nie J, Liu L, Zheng W, et al. microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2[J]. Carcinogenesis, 2012, 33(1): 220-225.
[6] Indovina P, Pentimalli F, Casini N, et al. RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy[J]. Oncotarget, 2015, 6(20): 17873-17890.
[7] Xanthoulis A, Tiniakos D G. E2F transcription factors and digestive system malignancies: how much do we know?[J]. World J Gastroenterol, 2013, 19(21): 3189-3198.
[8] Sun Q, Zhang Y, Yang G, et al. Transforming growth factor-beta-regulated miR-24 promotes skeletal muscle differentiation[J]. Nucleic Acids Res, 2008, 36(8): 2690-2699.
[9] Liu J, Zhang L, Lei J, et al. MicroRNA-responsive cancer cell imaging and therapy with functionalized gold nanoprobe[J]. ACS Appl Mater Interfaces, 2015, 7(34): 19016-19023.
[10] Zhang Z, Li Z, Li Y, et al. MicroRNA and signaling pathways in gastric cancer[J]. Cancer Gene Ther, 2014, 21(8): 305-316.
[11] Bai J, Zhang Z, Li X, et al. MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression[J]. Cancer Biomark, 2015, 15(5): 599-608.
[12] Bai J, Zhang Z, Li X, et al. MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression[J]. Int J Clin Exp Pathol, 2015, 8(5): 4913-4922.
[13] Chen Z, Huang Z, Ye Q, et al. Prognostic significance and anti-proliferation effect of microRNA-365 in hepatocellular carcinoma[J]. Int J Clin Exp Pathol, 2015, 8(2): 1705-1711.
[14] Kang S M, Lee H J, Cho J Y. MicroRNA-365 regulates NKX2-1, a key mediator of lung cancer[J]. Cancer Lett, 2013, 335(2): 487-494.
[15] Evangelou K, Havaki S, Kotsinas A. E2F transcription factors and digestive system malignancies: how much do we know?[J]. World J Gastroenterol, 2014, 20(29): 10212-10216.
[16] Iglesias-Ara A,Zenarruzabeitia O, Buelta L, et al. E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution[J]. Cell Death Differ, 2015, 22(10): 1577-1589.
[17] Zhang P, Zheng C, Ye H, et al. MicroRNA-365 inhibits vascular smooth muscle cell proliferation through targeting cyclin D1[J]. Int J Med Sci, 2014, 11(8): 765-770.
[18] Zhou L, Wang Y, Ou C, et al. microRNA-365-targeted nuclear factor I/B transcriptionally represses cyclin-dependent kinase 6 and 4 to inhibit the progression of cutaneous squamous cell carcinoma[J]. Int J Biochem Cell Biol, 2015, 65: 182-191.
[19] Guo S L, Ye H, Teng Y, et al. Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency[J]. Nat Commun, 2013, 4: 2544.
[20] Tong F, Cao P, Yin Y, et al. MicroRNAs in gastric cancer: from benchtop to bedside[J]. Dig Dis Sci, 2014, 59(1): 24-30.
[21] Kanat O, O'Neil B, Shahda S. Targeted therapy for advanced gastric cancer: A review of current status and future prospects[J]. World J Gastrointest Oncol, 2015, 7(12): 401-410.
[22] 李龙,李静,黄东兰,等. 胃癌患病风险关键基因筛选[J]. 中华肿瘤防治杂志,2014,21(2):95-99.
[23] 李立平,吴炜景,赵亚刚. microRNA与胃癌的研究进展[J]. 中华肿瘤防治杂志. 2013,20(4):312-316.

miR-365通过靶向E2F2抑制胃癌细胞增生和肿瘤形成

miR-365 inhibited the proliferation and tumorigenicity of gastric cancer cells by targeting E2F2

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	苏珈仪, 刘春涛, 王铁山, 李文坤, 杨奕, 武珊珊, 李鹏, 吴静. 血清幽门螺杆菌抗体分型检测与胃黏膜病变的相关性[J]. 首都医科大学学报, 2022, 43(2): 216-220.
[2]	马宗慧, 张倩, 邢洁, 朱圣韬, 李鹏, 张澍田, 孙秀静. 早期胃癌内镜下治疗的非治愈性切除率及影响因素[J]. 首都医科大学学报, 2022, 43(1): 17-21.
[3]	宁婷婷, 徐俊玄, 刘思, 闵力, 朱圣韬. TRIM28在胃癌中表达的临床意义及对胃癌细胞侵袭和迁移的影响[J]. 首都医科大学学报, 2020, 41(4): 570-575.
[4]	祁缘, 荆黎. microRNA-181b对心血管疾病的调控作用及机制的研究进展[J]. 首都医科大学学报, 2019, 40(3): 396-401.
[5]	宫鹏超, 李艳兰, 孔翠翠, 田昕. 蟾蜍灵通过程序性坏死途径诱导人胃癌细胞SGC-7901死亡[J]. 首都医科大学学报, 2019, 40(2): 251-256.
[6]	孙秀静, 张倩, 邢洁, 朱敏, 郭俊峰, 曹彬, 朱圣韬, 李鹏, 张澍田. 超声内镜对早期胃癌浸润深度的诊断价值及影响因素分析[J]. 首都医科大学学报, 2018, 39(5): 669-674.
[7]	蒲昌盛, 郑智, 蔡军, 唐华臻, 张军, 张忠涛. Siewert Ⅱ型食管胃结合部腺癌组织中PDZK1和PDGFR-β的表达及相互作用[J]. 首都医科大学学报, 2017, 38(6): 804-809.
[8]	王利娟, 杨春, 谷牧青, Pierre Hardy, 阮祥燕, Alfred O. Mueck. 受孕激素调节的microRNAs与乳腺癌的关系[J]. 首都医科大学学报, 2017, 38(4): 521-525.
[9]	王俊雄, 蔡习强, 聂勇战, 郝建宇, 樊代明. 血清饥饿激活表皮生长因子受体诱导胃癌耐药[J]. 首都医科大学学报, 2016, 37(1): 23-29.
[10]	魏华, 景红, 吴江, 张东航. 胃癌中葡萄糖调节蛋白78和葡萄糖调节蛋白94表达的临床意义及与预后的相关性[J]. 首都医科大学学报, 2014, 35(4): 501-506.
[11]	张瑞雪, 闫涵, 王民, 金启成, 杨薏帆, 曹邦伟. XELOX方案与FOLFOXs方案治疗中国晚期胃癌患者的Meta分析[J]. 首都医科大学学报, 2013, 34(3): 422-427.
[12]	孔曼, 裴文仲, 杨建东. 替吉奥联合奥沙利铂治疗进展期胃癌的临床疗效观察[J]. 首都医科大学学报, 2013, 34(3): 446-449.
[13]	孟倩;赵旭宏;赵瑾;雷婷;张曼. 消化道不同恶性肿瘤患者血清锌α-2-糖蛋白水平检测及临床意义[J]. 首都医科大学学报, 2012, 33(5): 665-668.
[14]	林晨曦;叶延程;张志镒;王军贤;梁晓云;刘玉琴;罗冰芝;邹珺;王涛. 甘肃武威地区农村出院胃癌患者生命质量及其影响因素研究[J]. 首都医科大学学报, 2011, 32(5): 661-666.
[15]	朱圣韬;曹邦伟;徐昌青;李琴;赵志海;李丹萍;张澍田. TIM-3基因启动子区多态性与胃癌易感的相关性研究[J]. 首都医科大学学报, 2010, 31(3): 299-303.