miR-99a对口腔鳞癌增殖能力的影响

doi:10.19439/j.sjos.2021.01.009

上海口腔医学 ›› 2021, Vol. 30 ›› Issue (1): 44-49.doi: 10.19439/j.sjos.2021.01.009

miR-99a对口腔鳞癌增殖能力的影响

王科, 彭国光, 谭玉莲, 何善志, 罗翠芬

广州中医药大学附属佛山市中医院口腔医疗中心,广东佛山 528000

收稿日期:2019-03-11 修回日期:2019-11-12 出版日期:2021-02-25 发布日期:2021-04-02
通讯作者: 彭国光,E-mail: guoguang828@yahoo.com.cn
作者简介:王科（1982-）,男,副主任医师,硕士研究生,E-mail: keke820403@163.com
基金资助:
佛山市医学重点专科培育项目（Fspy3-2015018）

MiR-99a inhibits proliferation of oral squamous cell carcinoma by targeting mTOR pathway

WANG Ke, PENG Guo-guang, TAN Yu-lian, HE Shan-zhi, LUO Cui-fen

Stomatological Medical Center of Foshan Traditional Chinese Medicine, Hospital Affiliated to Guangzhou University of Chinese Medicine. Foshan 528000, Guangdong Province, China

Received:2019-03-11 Revised:2019-11-12 Online:2021-02-25 Published:2021-04-02

摘要/Abstract

摘要： 目的:探讨miR-99a在口腔鳞状细胞中的表达及对口腔鳞癌细胞生物学行为的影响。方法:检索GEO 数据库中与口腔鳞癌相关的miRNA芯片进行二次分析。检测63 例口腔鳞癌组织和口腔鳞癌细胞株内miR-99a的表达,分析其与临床病理指标及患者预后之间的关系。上调miR-99a的表达,检测其对口腔鳞癌细胞生长和克隆形成的影响,并通过Targetscan等软件预测其靶基因。采用SPSS 19.0软件包对数据进行统计学分析。结果:GSE103931芯片显示,miR-99a在口腔鳞癌中下调最显著,且miR-99a也在口腔鳞癌细胞株内显著低表达。 miR-99a的表达与患者T分期、病理分级和预后密切相关。上调miR-99a的表达可抑制口腔鳞癌细胞增殖;而抑制miR-99a的表达,则促进口腔鳞癌细胞增殖。通过Targetscan等软件发现,mTOR是miR-99a的靶基因,且与miR-99a的表达呈负相关。结论:miR-99a在口腔鳞癌组织和细胞系中低表达。上调 miR-99a能抑制口腔鳞癌细胞株SCC25和SCC9的增殖能力, 其机制是通过调控mTOR的表达而实现。

关键词: miR-99a, 口腔鳞状细胞癌, mTOR, 细胞增殖

Abstract: PURPOSE: To investigate miR-99a expression and its effect on proliferation of oral squamous cell carcinoma (OSCC). METHODS: miRNA microarrays associated with OSCC were identified in GEO database. The expression levels of miR-99a were detected in 63 OSCC tissues and adjacent normal tissues and cell lines. The relationship between clinicopathological parameters and miR-99a expression was analyzed by using ANOVA analysis. The ability of cell growth and clone formation were examined in SCC9 and SCC25 cells transfected with miR-99a mimics. The target genes of miR-99a were predicted by Targetscan software. There resulting data were analyzed using SPSS 19.0 software package.RESULTS: The differently expressed miRNAs were analyzed based on GSE103931 microarray. miR-99a was significantly downregulated in OSCC tissues and cell lines. miR-99a expression was significantly associated with T stage, pathological grading and patients’ prognosis. miR-99a overexpression inhibited OSCC cell proliferation and clone formation, while miR-99a inhibition contributed to decreased proliferation and clone formation ability. In addition, miR-99a combined with mTOR gene’s 3’UTR was negatively correlated with mTOR expression in OSCC tissues. CONCLUSIONS: miR-99a functions as a tumor suppressor in OSCC and inhibits OSCC cell proliferation by targeting mTOR.

Key words: miR-99a, Oral squamous cell carcinoma, mTOR, Cell proliferation

中图分类号:

R739.8

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.

WANG Ke, PENG Guo-guang, TAN Yu-lian, HE Shan-zhi, LUO Cui-fen. MiR-99a inhibits proliferation of oral squamous cell carcinoma by targeting mTOR pathway[J]. Shanghai Journal of Stomatology, 2021, 30(1): 44-49.

参考文献

[1] Siegel RL, Miller KD, Jemal A.Cancer statistics, 2016[J]. CA Cancer J Clin, 2016, 66(1): 7-30.
[2] Bello IO, Soini Y, Salo T.Prognostic evaluation of oral tongue cancer: means, markers and perspectives[J]. Oral Oncol, 2010, 46(9): 630-635.
[3] Hussein AA, Helder MN, de Visscher JG, et al. Global incidence of oral and oropharynx cancer in patients younger than 45 years versus older patients: a systematic review[J]. Eur J Cancer, 2017, 82(1): 115-127.
[4] Shah JP, Gil Z.Current concepts in management of oral cancer-surgery[J]. Oral Oncol, 2009, 45(4-5): 394-401.
[5] Massano J, Regateiro FS, Januário G, et al.Oral squamous cell carcinoma: review of prognostic and predictive factors[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2006, 102(1): 67-76.
[6] Pereira CM, Sehnem D, da Fonseca EO, et al. miRNAs: important targets for oral cancer pain research[J]. Biomed Res Int, 2017:4043516.
[7] Yuan HL, Wang T, Zhang KH.MicroRNAs as potential biomarkers for diagnosis, therapy and prognosis of gastric cancer[J]. Onco Targets Ther, 2018, 11: 3891-3900.
[8] Garzon R, Fabbri M, Cimmino A, et al.MicroRNA expression and function in cancer[J]. Trends Mol Med, 2006, 12(12): 580-587.
[9] Tutar Y. miRNA and cancer; computational and experimental approaches[J]. Curr Pharm Biotechnol, 2014, 15(5): 429-438.
[10] Garzon R, Fabbri M, Cimmino A, et al.MicroRNA expression and function in cancer[J]. Trends Mol Med, 2006, 12(12): 580-587.
[11] Han Y, Li H. miRNAs as biomarkers and for the early detection of non-small cell lung cancer (NSCLC)[J]. J Thorac Dis, 2018, 10(5): 3119-3131.
[12] Lee E, Moon A.Identification of biomarkers for breast cancer using databases[J]. J Cancer Prev, 2016, 21(4): 235-242.
[13] Maimaiti A, Abudoukeremu K, Tie L, et al.MicroRNA expression profiling and functional annotation analysis of their targets associated with the malignant transformation of oral leukoplakia[J]. Gene, 2015, 558(2): 271-277.
[14] Cui J, Li D, Zhang W, et al.Bioinformatics analyses combined microarray identify the deregulated microRNAs in oral cancer[J]. Oncol Lett, 2014, 8(1): 218-222.
[15] Wang Q, Lv L, Li Y, et al.MicroRNA-655 suppresses cell proliferation and invasion in oral squamous cell carcinoma by directly targeting metadherin and regulating the PTEN/AKT pathway[J]. Mol Med Rep, 2018, 18(3): 3106-3114.
[16] Yu ZW, Zhong LP, Ji T, et al.MicroRNAs contribute to the chemoresistance of cisplatin in tongue squamous cell carcinoma lines[J]. Oral Oncol, 2010, 46(4): 317-322.
[17] Lo WL, Yu CC, Chiou GY, et al.MicroRNA-200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells[J]. J Pathol, 2010, 223(4): 482-495.
[18] Sun M, Hong S, Li W, et al.MiR-99a regulates ROS-mediated invasion and migration of lung adenocarcinoma cells by targeting NOX4[J]. Oncol Rep, 2016, 35(5): 2755-2766.
[19] Wang L, Chang L, Li Z, et al.MiR-99a and -99b inhibit cervical cancer cell proliferation and invasion by targeting mTOR signaling pathway[J]. Med Oncol, 2014, 31(5): 934-940.
[20] Wu D, Zhou Y, Pan H, et al.MicroRNA-99a inhibiting cell proliferation, migration and invasion by targeting fibroblast growth factor receptor 3 in bladder cancer[J]. Oncol Lett, 2014, 7(4): 1219-1224.
[21] Li X, Zhang Y Zhang H, et al. MiRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3[J]. Mol Cancer Res, 2011, 9(7) : 824-833.
[22] Zhang L, Li X, Ke Z, et al.MiR-99a may serve as a potential oncogene in ediatric myeloid leukemia[J]. Cancer Cell Int, 2013, 13(1) : 110-117.
[23] Duval AP, Jeanneret C, Santoro T, et al.mTOR and tumor cachexia[J]. Int J Mol Sci, 2018, 19(8): 2225-2233.
[24] Kawasaki G, Naruse T, Furukawa K, et al.mTORC1 and mTORC2 expression levels in oral squamous cell carcinoma: an immunohistochemical and clinicopathological study[J]. Anticancer Res, 2018, 38(3): 1623-1628.
[25] Chen TC, Wu CT, Wang CP, et al.Significance of nuclear p-mTOR expression in advanced oral squamous cell carcinoma with extracapsular extension of lymph node metastases[J]. Oral Oncol, 2015, 51(5): 493-499.

miR-99a对口腔鳞癌增殖能力的影响

MiR-99a inhibits proliferation of oral squamous cell carcinoma by targeting mTOR pathway

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]	陈祺, 谢非, 季颖颖, 魏魁杰, 任强. LLY-283靶向PRMT5抑制头颈部鳞癌增殖和转移的实验研究[J]. 上海口腔医学, 2022, 31(2): 142-147.
[2]	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.
[3]	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.
[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]	曹颖, 彭伟伟, 王璇, 伍甜甜, 杜嵘, 朱亚琴. 重组人结缔组织生长因子对牙髓细胞增殖与成牙本质分化的影响[J]. 上海口腔医学, 2020, 29(1): 7-12.
[7]	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.
[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.
[9]	冯小东, 易文, 殷卫红. 过表达miR-218对舌鳞癌细胞系SCC-4和SCC-9的增殖和侵袭的影响[J]. 上海口腔医学, 2019, 28(4): 373-377.
[10]	张漫, 李昊, 徐婷, 刘杰, 谈飞. 含锶交联藻酸钠凝胶对前成骨细胞黏附和增殖的影响[J]. 上海口腔医学, 2019, 28(2): 123-127.
[11]	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.
[12]	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.
[13]	高锦瑜, 余小琴, 王军强. 周期性牵张应力作用下KLF5对人牙周膜细胞增殖和成骨分化的影响[J]. 上海口腔医学, 2018, 27(1): 28-33.
[14]	李凤霞, 王俊, 马玉云. CCN3调控牙周膜成纤维细胞的增殖和凋亡[J]. 上海口腔医学, 2017, 26(5): 504-509.
[15]	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.