miRNA-101在甲状腺髓样癌中抑癌机制的研究

doi:10.12092/j.issn.1009-2501.2018.05.007

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (5): 524-530.doi: 10.12092/j.issn.1009-2501.2018.05.007

miRNA-101在甲状腺髓样癌中抑癌机制的研究

徐明，崔鹏，叶敏，倪熊，王廷峰，闵志钧

上海市浦东医院，复旦大学附属浦东医院，普外科，浦东 201300，上海

收稿日期:2017-10-20 修回日期:2018-02-25 出版日期:2018-05-26 发布日期:2018-05-16
通讯作者: 闵志钧，男，本科，主任医师，研究方向：甲状腺/胃肠外科。
作者简介:徐明，男，本科，副主任医师，研究方向：甲状腺/胃肠外科。 Tel：021-68035123 E-mail：3033962870@qq.com
基金资助:
上海市卫生和计划生育委员会科研项目（201440467）

Insights into tumor suppression mechanism of miRNA-101 in medullary thyroid carcinoma

XU Ming, CUI Peng, YE Min, NI Xiong, WANG Tingfeng, MIN Zhijun

Department of General Surgery, Shanghai Pudong Hospital, Pudong Hospital Affiliated to Fudan University, Shanghai 201300, China

Received:2017-10-20 Revised:2018-02-25 Online:2018-05-26 Published:2018-05-16

摘要/Abstract

摘要：

目的:研究microRNA-101在甲状腺髓样细胞中的抑癌机制。方法:首先用荧光定量PCR技术检测甲状腺髓样癌组织中microRNA-101的表达。接着采用microRNA-101模拟物干预法，并用流式细胞仪技术，Transwell实验等方法，对实验组和对照组细胞的增殖、迁移和凋亡进行比较。此外，还通过Western blot、报告基因检测法、流式细胞仪技术和Transwell实验确定miRNA-101靶基因以及相应的抑癌机制。结果:miRNA-101在甲状腺髓样癌组织中的表达相比癌旁组织下调（P<0.01）。与阴性对照组相比，miRNA-101模拟物转染组的甲状腺髓样癌细胞的增殖和迁移受到显著抑制，而凋亡率显著提高。Western blot和荧光素酶报告实验证实SOX9基因是miRNA-101下游的靶基因并被其下调。SOX9基因敲除可抑制甲状腺髓样癌细胞增殖，迁移和促进癌细胞凋亡。结论:microRNA-101通过靶向下调SOX9基因的表达抑制甲状腺髓样癌细胞的增殖和迁移，加速甲状腺髓样癌细胞的凋亡。

关键词: 甲状腺髓样癌细胞, microRNA-101, SOX9

Abstract:

AIM: To explore the tumor suppression mechanism of microRNA-101 in human medullary thyroid carcinoma cells (TT cells). METHODS: The expression of microRNA-101 in tissue samples from patients with medullary thyroid carcinoma was analyzed by quantitative RT-PCR. Then TT cells were divided into two groups and transfected with miRNA-101 mimics/ negative control. Flow cytometry and Transwell assay were used to detect TT cell cycle distribution, apoptotic rate as well as cell migration. Moreover, Western blot, flow cytometry, luciferase and Transwell assays were used to predict target gene of miRNA-101 as well as its underlying mechanism. RESULTS: MiRNA-101 was significantly down-regulated in medullary thyroid carcinoma tissues. MiRNA-101 mimics' transfection significantly inhibited TT cell proliferation and migration, induced cell apoptosis comparing with negative control. Western blot and luciferase assay revealed that SOX9 gene expression was down-regulated by miRNA-101. Silencing of SOX9 by siRNA showed similar effects with miRNA-101 over-expression. CONCLUSION: MicroRNA-101 inhibits proliferation, migration and induces apoptosis of human medullary thyroid carcinoma cells by targeting SOX9 gene.

Key words: medullary thyroid carcinoma cells, microRNA-101, SOX9

中图分类号:

R965.2

徐明，崔鹏，叶敏，倪熊，王廷峰，闵志钧. miRNA-101在甲状腺髓样癌中抑癌机制的研究[J]. 中国临床药理学与治疗学, 2018, 23(5): 524-530.

XU Ming, CUI Peng, YE Min, NI Xiong, WANG Tingfeng, MIN Zhijun. Insights into tumor suppression mechanism of miRNA-101 in medullary thyroid carcinoma[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 524-530.

参考文献

［1］Hazard JB, Hawk WK, Crile G Jr. Medullary (solid) carcinoma of the thyroid-a clinicopathologic entity［J］. J Clin Endocrinol Metab, 1959, 19(1): 152-161.
［2］黄彩平, 朱永学, 田敖龙. 147例甲状腺髓样癌临床分析［J］. 中华肿瘤杂志, 2003, 25(5): 490-492.
［3］Lee RC, Feinbaum RL, Ambros V,et al. Elegans heterochromic gene Lin-4 encodes small RNAs with antisense complementarity to Lin-14［J］. Cell, 1993, 75(5): 843-845.
［4］Kozomara A, GriffithsJones S. miRBase: annotating high confidence microRNAs using deep sequencing data［J］. Nucleic Acids Res, 2014, 42: 68-73.
［5］Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues［J］. Oncogene, 2006, 25(17): 2537-2545.
［6］Lowery A J, Miller N, Devaney A, et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER/neu receptor status in breast cancer［J］. Breast Cancer Res, 2009, 11(3): R27.
［7］Yanaihara N, Caplen N, Bowman E, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis［J］. Cancer Cell. 2006, 9(3): 189-198.
［8］Ratert N, Meyer HA, Jung M, et al. miRNA profiling identifies candidate mirnas for bladder cancer diagnosis and clinical outcome［J］. J Mol Diagn. 2013, 15(5): 695-705.
［9］Corte H, Manceau G, Blons H, et al. MicroRNA and colorectal cancer［J］. Dig Liver Dis. 2012, 44(3): 195200.
［10］胡明珠, 李佩玲. 非编码RNA在卵巢癌中的研究进展［J］. 疑难病杂志, 2016, 15(11): 1197-1200, 1205.
［11］Abraham D, Jackson N, Gundara JS, et al. MicroRNA profiling of sporadic and hereditary medullary thyroid cancer identifies predictors of nodal metastasis, prognosis, and potential therapeutic targets［J］. Clin Cnacer Res, 2011, 17(4): 4772-4781.
［12］Pennelli G, Galuppini F, Barollo S, et al. The PDCD4/miR-21 pathway in medullary thyroid carcinoma［J］. Hum Pathol. 2015, 46(1): 50-57.
［13］Hudson JH, Duncavage E, Tamburrino A, et al. Overexpression of miR-10a and miR-375 and downregulation of YAP1 in medullary thyroid carcinoma［J］. Exp Mol Pathol, 2013, 95(1): 62-67.
［14］Duan L, Hao X, Liu Z, et al. MiR-129-5p is down-regulated and involved in the growth, apoptosis and migration of medullary thyroid carcinoma cells through targeting RET［J］. FEBS Lett, 2014, 588(9): 1644-1651.
［15］Su H, Yang J R, Xu T, et al. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity［J］. Cancer Res, 2009, 69(3): 1135-1142.
［16］ Cho HM, Jeon HS, Lee SY, et al. microRNA-101 inhibits lung cancer invasion through the regulation of enhancer of zeste homolog 2［J］. Exp Ther Med, 2011, 2(5): 963-967.
［17］Chakravarthi BVSK, Goswami MT, Pathi SS, et al. MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer［J］. Oncogene, 2016, 35(49): 6330-6340.
［18］Huang F, Lin C, Shi YH, et al. MicroRNA-101 inhibits cell proliferation, invasion, and promotes apoptosis by regulating cyclooxygenase-2 in Hela cervical carcinoma cells［J］. Asian Pac J Cancer Prev, 2013, 14(10): 5915-5920.
［19］Long Y, Wu Z, Yang X, et al. MicroRNA-101 inhibits the proliferation and invasion of bladder cancer cells via targeting c-FOS［J］. Mol Med Rep, 2016, 14(3): 2651-2656.
［20］Wang C, Lu S, Jiang J, et al. HsamicroRNA101 suppresses migration and invasion by targeting Rac1 in thyroid cancer cells［J］. Oncology Lett, 2014, 8(4): 1815-1821.
［21］陈维, 王昌留, 王磊. SOX9基因的结构、功能及进化［J］. 生命的化学, 2012, 32(4): 310-315.
［22］Zhang Y, Guo X, Xiong L, et al. MicroRNA-101 suppresses SOX9-dependent tumorigenicity and promotes favorable prognosis of human hepatocellular carcinoma［J］. FEBS Lett, 2012, 586(24): 4362-4370.
［23］Liu N, Zhang L, Wang Z, et al. MicroRNA-101 inhibits proliferation, migration and invasion of human glioblastoma by targeting SOX9［J］. Oncotarget, 2017, 8(12): 19244-19254.

[1]	曹雪芬, 冷玉芳, 韩晓霞, 侯小煜, 吕兴娇, Janvier NIBARUTA. 川芎嗪通过抑制NLRP3减轻肠缺血再灌注损伤的细胞焦亡[J]. 中国临床药理学与治疗学, 2023, 28(11): 1201-1208.
[2]	王剑, 孙永东, 周兴玮, 刘雷, 陈龙, 童兴科, 朱佳丽. 黄芩素经由miR-125b-5p/IRF4轴进而促进喉癌细胞死亡并抑制其侵袭的机制研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1209-1218.
[3]	朱瑞芳, 郭东凯, 智慧, 江翊国, 张悦翎, 钱晓萍, 季士亮. ROS-NF-κB-p38MAPK通路探索榄香烯联合硼替佐米抗多发性骨髓瘤的机制研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1219-1226.
[4]	李菲, 丁慧琴, 陈梦静. 异莲心碱激活ERK信号通路诱导肺癌PC9细胞自噬的作用研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1235-1240.
[5]	石丹丹, 孙祎尧, 陈晓琦, 杨芳明, 张传雷, 王新亭, 袁长威, 陈欣菊. 扶正消瘤颗粒治疗原发性肝癌的疗效观察及血清代谢组学分析[J]. 中国临床药理学与治疗学, 2023, 28(11): 1247-1262.
[6]	陈玉林, 蒋虎刚, 王新强, 刘凯, 李应东, 安涛, 赵信科. 基于网络药理学和分子对接探讨芪参益心颗粒治疗射血分数保留型心力衰竭的作用机制[J]. 中国临床药理学与治疗学, 2023, 28(10): 1081-1092.
[7]	王秀, 季麒麟, 裴文俊, 曾颖. 3-溴丙酮酸-胆固醇酯增强乳腺癌细胞对他莫昔芬敏感性研究[J]. 中国临床药理学与治疗学, 2023, 28(10): 1093-1100.
[8]	衡冰冰, 杨丹峰, 戴舒阳, 上官王宁. 丙泊酚对皮下注射氯喹所致瘙痒大鼠脊髓TRPV1和CB1受体的影响[J]. 中国临床药理学与治疗学, 2023, 28(10): 1101-1108.
[9]	廖梦玲, 汪艳, 罗静, 王诺妍, 华玲, 张瑜, 邓非, 袁月, 周军, 周红. 青蒿琥酯抑制巨噬细胞释放前炎症细胞因子的分子作用机制研究[J]. 中国临床药理学与治疗学, 2023, 28(9): 969-978.
[10]	游蓉丽, 黄玉荣, 毛睿, 海丽娜, 王颖莉, 王艳. 基于血清代谢组学与网络药理学探究复方苦参注射液治疗肺癌的作用机制[J]. 中国临床药理学与治疗学, 2023, 28(9): 988-999.
[11]	王如玥, 谢飞, 王欣, 李红玉. 脾多肽注射液对化疗后KM小鼠骨髓抑制和免疫力低下的治疗作用[J]. 中国临床药理学与治疗学, 2023, 28(9): 1000-1007.
[12]	毛君, 荣玉, 李炎根, 熊登喜, 赵鹏, 查正江. 氟比洛芬酯在颅脑损伤患者镇痛治疗中的临床应用效果观察及安全性分析[J]. 中国临床药理学与治疗学, 2023, 28(9): 1056-1060.
[13]	马仙康, 杨丽霞, 崔阳阳, 米登海. 当归多糖通过抑制GRP78、p-PERK、p-Eif2α表达改善糖尿病KK-Ay小鼠肝内质网应激[J]. 中国临床药理学与治疗学, 2023, 28(8): 926-936.
[14]	王坤, 许佩佩, 周兰兰, 鲁晟. 人参皂苷Rg1调控Epac1/Rap1信号通路对缺血性脑卒中大鼠神经保护作用机制研究[J]. 中国临床药理学与治疗学, 2023, 28(7): 721-727.
[15]	李士旭, 李林运, 王新, 李轲, 卞华. 银杏叶提取物通过miR-145/FOXO1轴对实验性肾功能衰竭大鼠肾脏损伤的影响[J]. 中国临床药理学与治疗学, 2023, 28(7): 728-735.

miRNA-101在甲状腺髓样癌中抑癌机制的研究

Insights into tumor suppression mechanism of miRNA-101 in medullary thyroid carcinoma

PDF (PC)

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