LncTUG1通过靶向miR-212-3p对口腔鳞状细胞癌细胞NK细胞杀伤敏感性的影响

doi:10.19439/j.sjos.2019.06.002

上海口腔医学 ›› 2019, Vol. 28 ›› Issue (6): 567-571.doi: 10.19439/j.sjos.2019.06.002

LncTUG1通过靶向miR-212-3p对口腔鳞状细胞癌细胞NK细胞杀伤敏感性的影响

王培¹, 汤春波², 李斌¹, 傅宗云¹

1.东南大学附属中大医院口腔科,江苏南京 210009;
2.江苏省口腔医院口腔种植科,江苏南京 210029

收稿日期:2019-04-30 出版日期:2019-12-25 发布日期:2020-01-14
通讯作者: 王培,E-mail：1173792604@qq.com
作者简介:王培（1991-）,男,硕士,住院医师
基金资助:
国家自然科学基金（81470778）

Effect of LncTUG1 on NK cell killing sensitivity in oral squamous cell carcinoma cells by targeting miR-212-3p

WANG Pei¹, TANG Chun-bo², LI Bin¹, FU Zong-yun¹

1.Department of Stomatology, Zhongda Hospital Affiliated to Southeast University. Nanjing 210009;
2.Department of Dental Implantation, Jiangsu Stomatological Hospital. Nanjing 210029, Jiangsu Province, China

Received:2019-04-30 Online:2019-12-25 Published:2020-01-14

摘要/Abstract

摘要： 目的探讨长链非编码RNA（Lnc）牛磺酸调节基因1(taurine up-regulated gene 1,TUG1)对口腔鳞状细胞癌细胞自然杀伤细胞(nature killer cell, NK)杀伤敏感性的影响。方法以口腔鳞状细胞癌细胞作为体外实验对象,转染TUG1 siRNA,利用qRT-PCR、MTT、流式细胞术、LDH方法,分别检测TUG1表达量、细胞增殖、细胞凋亡和NK细胞杀伤率。利用生物信息学软件预测TUG1与miR-212-3p靶向互补结合,构建荧光素酶报告载体,鉴定靶向关系。在口腔鳞状细胞癌细胞中共转染TUG1 siRNA和miR-212-3p 抑制剂,评估miR-212-3p 抑制剂对TUG1 siRNA影响口腔鳞状细胞癌细胞增殖凋亡和NK细胞杀伤敏感性的影响。采用SPSS 21.0软件包对实验数据进行统计学分析。结果 TUG1 siRNA可显著降低口腔鳞状细胞癌细胞中TUG1的表达水平（P=0.000）,降低细胞增殖能力（P=0.001）,促进细胞凋亡（P=0.000）,增加NK细胞杀伤率（P<0.01）。TUG1 siRNA靶向提高miR-212-3p表达量。miR-212-3p 抑制剂可逆转TUG1 siRNA对口腔鳞状细胞癌细胞增殖、凋亡和NK细胞杀伤率的影响。结论下调TUG1可靶向负调控miR-212-3p,抑制口腔鳞状细胞癌细胞增殖并诱导凋亡,提高NK细胞杀伤敏感性。

关键词: 口腔鳞状细胞癌, NK细胞杀伤敏感性, miR-212-3p, TUG1

Abstract: PURPOSE: To investigate the effect of LncTUG1 on NK cell killing sensitivity in oral squamous cell carcinoma cells. METHODS: Oral squamous cell carcinoma cells were used as experimental objects in vitro. TUG1 siRNA was transfected,the expression of TUG1, cell proliferation, cell apoptosis and NK cell killing rate were detected by qRT-PCR, MTT, flow cytometry and LDH. Bioinformatics software was used to predict that TUG1 and miR-212-3p will target and complement each other, so luciferase reporter vector was constructed and the targeting relationship was identified. TUG1 siRNA and miR-212-3p inhibitor were co-transfected into oral squamous cell carcinoma cells, the effects of miR-212-3p inhibitor on TUG1 siRNA on proliferation, apoptosis and NK cell killing sensitivity of oral squamous cell carcinoma cells were evaluated. The data were analyzed with SPSS 21.0 software package. RESULTS: TUG1 siRNA could significantly reduce the expression of TUG1 in oral squamous cell carcinoma cells (P=0.000), decrease cell proliferation (P=0.001), promote cell apoptosis (P=0.000), increase the killing rate of NK cells (P<0.01). TUG1 siRNA targeted to increase the expression of miR-212-3p. miR-212-3p inhibitor could reverse the effects of TUG1 siRNA on proliferation, apoptosis and NK cell killing rate of oral squamous cell carcinoma cells. CONCLUSIONS: Down-regulation of TUG1 targeting and negative regulation of miR-212-3p inhibits proliferation, induces apoptosis and improves NK cell killing sensitivity of oral squamous cell carcinoma cells.

Key words: Oral squamous cell carcinoma, NK cell killing sensitivity, Mi-212-3p, TUG1

中图分类号:

R739.8

王培, 汤春波, 李斌, 傅宗云. LncTUG1通过靶向miR-212-3p对口腔鳞状细胞癌细胞NK细胞杀伤敏感性的影响[J]. 上海口腔医学, 2019, 28(6): 567-571.

WANG Pei, TANG Chun-bo, LI Bin, FU Zong-yun. Effect of LncTUG1 on NK cell killing sensitivity in oral squamous cell carcinoma cells by targeting miR-212-3p[J]. Shanghai Journal of Stomatology, 2019, 28(6): 567-571.

参考文献

[1] Satgunaseelan L, Gupta R, Madore J, et al.Programmed cell death-ligand 1 expression in oral squamous cell carcinoma is associated with an inflammatory phenotype[J]. Pathology, 2016, 48(6): 574-580.
[2] Jiang C, Yuan F, Wang J, et al.Oral squamous cell carcinoma suppressed antitumor immunity through induction of PD-L1 expression on tumor-associated macrophages[J]. Immunobiology, 2016, 222(4): 651-657.
[3] Lasfar A, de laTorre A, Abushahba W, et al. Concerted action of IFN-α and IFN-λ induces local NK cell immunity and halts cancer growth[J]. Oncotarget, 2016, 7(31): 49259-49267.
[4] Zhang E, He X, Yin D, et al.Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57[J]. Cell Death Dis, 2016, 7: e2109.
[5] Li T, Liu Y, Xiao H, et al.Long non-coding RNA TUG1 promotes cell proliferation and metastasis in human breast cancer[J]. Breast Cancer, 2016, 24(4): 535-543.
[6] Iliev R, Kleinova R, Juracek J, et al.Overexpression of long non-coding RNA TUG1 predicts poor prognosis and promotes cancer cell proliferation and migration in high-grade muscle-invasive bladder cancer[J]. Tumour Biol, 2016, 37(10): 13385-13390.
[7] Yang S, Ning Q, Zhang G, et al.Construction of differential mRNA-lncRNA crosstalk networks based on ceRNA hypothesis uncover key roles of lncRNAs implicated in esophageal squamous cell carcinoma[J]. Oncotarget, 2016, 7(52): 85728-85740.
[8] Qiu M, Feng D, Zhang H, et al.Comprehensive analysis of lncRNA expression profiles and identification of functional lncRNAs in lung adenocarcinoma[J]. Oncotarget, 2016, 7(13): 16012-16022.
[9] Lu Z, Pannunzio NR, Greisman HA, et al.Convergent BCL6 and lncRNA promoters demarcate the major breakpoint region for BCL6 translocations[J]. Blood, 2015, 126(14): 1730-1731.
[10] Jiang H, Hu X, Zhang H, et al.Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression[J]. Radiat Oncol, 2017, 12(1): 65.
[11] Xu Y, Wang J, Qiu M, et al.Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma[J]. Tumour Biol, 2015, 36(3): 1643-1651.
[12] Zhang Q, Geng PL, Yin P, et al.Down-regulation of Long Non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis[J]. Asian Pac J Cancer Prev, 2013, 14(4): 2311-2315.
[13] Yan G, Wang X, Yang M, et al.Long non-coding RNA TUG1 promotes progression of oral squamous cell carcinoma through upregulating FMNL2 by sponging miR-219[J]. Am J Cancer Res, 2017, 7(9): 1899-1912.
[14] Zhang G, Zhao H, Wu J, et al.Adoptive immunotherapy for non-small cell lung cancer by NK and cytotoxic T lymphocytes mixed effector cells: Retrospective clinical observation[J]. Int Immunopharmacol, 2014, 21(2): 396-405.
[15] Bellora F, Castriconi R, Dondero A, et al.TLR activation of tumor-associated macrophages from ovarian cancer patients triggers cytolytic activity of NK cells[J]. Eur J Immunol, 2014, 44(6):1814-1822.
[16] Wang Z, Zhu J, Gu H, et al.The clinicalsignificance of abnormal Tim-3 expression on NK cells from patients with gastric cancer[J]. Immunol Invest, 2015, 44(6): 578-589.
[17] Wang P, Chen D, Ma H, et al.LncRNA SNHG12 contributes to multidrug resistance through activating the MAPK/Slug pathway by sponging miR-181a in non-small cell lung cancer[J]. Oncotarget, 2017, 8(48): 84086-84101.
[18] Li Z, Dong M, Fan D, et al.LncRNA ANCR down-regulation promotes TGF-β-induced EMT and metastasis in breast cancer[J]. Oncotarget, 2017, 8(40): 67329-67343.
[19] Li H, Tian G, Tian F, et al.Long non coding RNA TUG1 promotes osteosarcoma cell proliferation and invasion through inhibition of microRNA 212 3p expression[J]. Exp Ther Med, 2018, 16(2): 779-787.
[20] Xia L, Li D, Lin C, et al.Comparative study of joint bioinformatics analysis of underlying potential of 'neurimmiR', miR-212-3P/miR-132-3P, being involved in epilepsy and its emerging role in human cancer[J]. Oncotarget, 2017, 8(25): 40668-40682.

LncTUG1通过靶向miR-212-3p对口腔鳞状细胞癌细胞NK细胞杀伤敏感性的影响

Effect of LncTUG1 on NK cell killing sensitivity in oral squamous cell carcinoma cells by targeting miR-212-3p

PDF (PC)

可视化

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]	陈娟, 曹若妍, 刘洋, 洪鹏宇, 唐瞻贵. TNFAIP6在口腔疣状癌与口腔鳞状细胞癌中的表达及其与临床病理的关系[J]. 上海口腔医学, 2022, 31(2): 167-172.
[2]	靳能皓, 南欣荣, 闫星泉. BTG1在78例口腔鳞癌中的表达及临床意义[J]. 上海口腔医学, 2021, 30(2): 140-144.
[3]	王科, 彭国光, 谭玉莲, 何善志, 罗翠芬. miR-99a对口腔鳞癌增殖能力的影响[J]. 上海口腔医学, 2021, 30(1): 44-49.
[4]	黄丹妮, 陈文鑫, 熊浩峰, 胡鑫, 毛婷, 苏彤. 口腔鳞状细胞癌患者术后服用二甲双胍对预后的影响[J]. 上海口腔医学, 2021, 30(1): 61-65.
[5]	郑晶, 李天客, 包阳, 张素欣. Spindly和Bub3在口腔鳞状细胞癌中的表达及意义[J]. 上海口腔医学, 2020, 29(5): 528-532.
[6]	达雨, 杨震, 夏苗苗, 王梦佳. Ki-67、PI3K、Beclin1在口腔鳞癌组织中的表达及意义[J]. 上海口腔医学, 2020, 29(1): 75-79.
[7]	杨宗澄, 黄海燕, 徐欣. 长链非编码RNA PCAT-1在口腔鳞状细胞癌中的表达及临床意义[J]. 上海口腔医学, 2019, 28(1): 67-70.
[8]	涂敏松, 李逸松, 张雄. YAP、TAZ蛋白在口腔鳞状细胞癌中的表达及意义[J]. 上海口腔医学, 2018, 27(4): 415-418.
[9]	李少明, 高岭, 任文豪, 薛令法, 许尧祥, 岳金, 郅克谦. 功能性与根治性颈淋巴清扫术在早期口腔鳞状细胞癌治疗中的疗效比较[J]. 上海口腔医学, 2017, 26(3): 305-308.
[10]	吴宁, 陆瑛, 梁继宗. Survivin和hsa-miR-542-3p在口腔鳞状细胞癌中的表达和相关性分析[J]. 上海口腔医学, 2016, 25(6): 720-724.
[11]	蒋丽兰, 赵娅军, 李勇. TGF-βRⅡ和NF-κB在口腔鳞状细胞癌的表达及临床意义[J]. 上海口腔医学, 2016, 25(6): 729-733.
[12]	谭丹, 黎春晖, 聂敏海. 细胞角蛋白19在口腔鳞状细胞癌中的表达及意义[J]. 上海口腔医学, 2016, 25(5): 600-603.
[13]	全海英,周丽佳,李昂迪,张泽兵. 氯喹增强口腔癌CAL-27细胞对顺铂化疗敏感性的观察[J]. 上海口腔医学, 2015, 24(1): 30-36.
[14]	顾文莉,叶冬霞,吴静静. microRNA-125b 在口腔鳞状细胞癌患者血浆中的表达及意义[J]. 上海口腔医学, 2015, 24(1): 71-75.
[15]	王璇, 黄绍辉, 於丽乔, 刘洁, 刁尧, 孙长伏. DEK原癌基因与口腔鳞状细胞癌的关系[J]. 上海口腔医学, 2014, 23(1): 75-79.