miR-214在口腔鳞状细胞癌中的表达及功能研究

中国口腔颌面外科杂志 ›› 2016, Vol. 14 ›› Issue (2): 97-105.

• 论著 • 下一篇

miR-214在口腔鳞状细胞癌中的表达及功能研究

吴越^{1, 2}, 王成^{1, 2}, 谢楠^{1, 3}, 庄泽航^{1, 2}, 刘习强^{1, 2}, 侯劲松^{1, 2}, 黄洪章^{1, 2}

1. 中山大学光华口腔医学院·附属口腔医院口腔颌面外科,广东广州 510055;
2. 广东省口腔医学重点实验室,广东广州 510055;
3. 中山大学光华口腔医学院·附属口腔医院口腔病理科,广东广州 510055

收稿日期:2015-11-19 出版日期:2016-03-20 发布日期:2016-04-06
通讯作者: 黄洪章,Tel:020-83860121,E-mail:huanghongzhang@tom.com
作者简介:吴越（1989-）,女,硕士,E-mail:wuhuaguo1989@126.com
基金资助:
国家自然科学基金（81272949,81572661,81202136）; 高等学校博士学科点专项科研基金（20120171120068）; 广州市珠江科技新星专项（2014J2200045）; 中央高校基本科研业务费专项资金中山大学青年教师培育计划（11ykpy47）

Expression and functional role of miR-214 in oral squamous cell carcinoma

WU Yue^{1, 2}, WANG Cheng^{1, 2}, XIE Nan^{1, 3}, ZHUANG Ze-hang^{1, 2}, LIU Xi-qiang^{1, 2}, HOU Jin-song^{1, 2}, HUANG Hong-zhang^{1, 2}

1.Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat -sen University. Guangzhou 510055; 2.Guangdong Provincial Key Laboratory. Guangzhou 510055; 3.Department of Oral Pathology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat -sen University. Guangzhou 510055, Guangdong Province, China

Received:2015-11-19 Online:2016-03-20 Published:2016-04-06

摘要/Abstract

摘要： 目的:探讨miR-214在口腔鳞状细胞癌中的表达及其对口腔鳞癌细胞侵袭、迁移、增殖和凋亡能力的影响。方法:实时荧光定量RT-PCR检测31例口腔鳞状细胞癌组织和7株口腔鳞状细胞癌细胞系中miR-214表达水平,分析其与患者临床病理参数的相关性;评估miR-214在7株细胞系中的基础表达水平,分别选择miR-214高、低表达的细胞系进行后续研究。对选择的细胞系分别转染miR-214 mimics和inhibitors,采用划痕实验、Transwell实验、流式细胞仪分别检测转染后细胞侵袭、迁移、增殖和凋亡能力的变化。采用SPSS19.0软件包对数据进行统计学处理。结果:在口腔鳞状细胞癌中,miR-214的表达与患者颈淋巴结转移情况和临床分期呈正相关（P<0.05）;转染miR-214 mimics的UM1细胞侵袭、迁移能力显著高于对照组（P<0.05）,转染miR-214 inhibitors的SCC9细胞侵袭、迁移能力显著低于对照组（P<0.05）;转染miR-214 mimics的UM1细胞周期阻滞在G1期,凋亡水平无明显变化,转染miR-214 inhibitors的SCC9细胞凋亡水平和细胞周期无明显变化。结论:miR-214与口腔鳞状细胞癌恶性表型相关,可增强口腔鳞状细胞癌细胞的侵袭和迁移能力。

关键词: miR-214, 口腔鳞癌, 侵袭, 迁移

Abstract: PURPOSE: To evaluate the expression of miR-214 and investigate its functional role in oral squamous cell carcinoma (OSCC). METHODS: RT-PCR was performed to detect miR-214 expression levels in 31 OSCC tissues and 7 OSCC cell lines. The correlation of miR-214 expression with the clinicopathologic features of the patients was analyzed with Chi-square test. Then, OSCC cells were transfected with miR-214 mimics and inhibitors. Wound healing assay and Transwell assay were performed to determine cell migratory and invasive abilities. Flow cytometry was used to assess cell cycle and apoptosis. SPSS19.0 software package was used for statistical analysis. RESULTS: In 31 OSCC patients, the expression of miR-214 positively correlated with lymph node metastasis and clinical stage (P<0.05). In vitro, the invasion and migration abilities were substantially enhanced in UM1 cells (P<0.05) transfected with miR-214 mimics and decreased (P<0.05) in SCC9 cells transfected with miR-214 inhibitors. Cell cycle was arrested in G1 stage but the apoptosis was not significantly increased in UM1 cells treated with miR-214 mimics. However, there were no obvious changes on cell cycle and apoptosis in SCC9 cells treated with miR-214 inhibitors. CONCLUSIONS: miR-214 is correlated with cervical lymph node metastasis and clinical stage in OSCC. It may act as an oncomiRNA to promote invasion and migration in OSCC.

Key words: miR-214, Oral squamous cell carcinoma, Invasion, Migration

中图分类号:

R739.8

吴越, 王成, 谢楠, 庄泽航, 刘习强, 侯劲松, 黄洪章. miR-214在口腔鳞状细胞癌中的表达及功能研究[J]. 中国口腔颌面外科杂志, 2016, 14(2): 97-105.

WU Yue, WANG Cheng, XIE Nan, ZHUANG Ze-hang, LIU Xi-qiang, HOU Jin-song, HUANG Hong-zhang. Expression and functional role of miR-214 in oral squamous cell carcinoma[J]. China J Oral Maxillofac Surg, 2016, 14(2): 97-105.

参考文献

[1] Leemans CR, Braakhuis BJM, Brakenhoff RH. The molecular biology of head and neck cancer[J]. Nat Rev Cancer,2010,11(1):9-22.
[2] Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011： the impact of eliminating socioeconomic and racial disparities on premature cancer deaths[J]. CA Cancer J Clin,2011,61(4):212-236.
[3] Scanlon CS, Van Tubergen EA, Inglehart RC, et al. Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma[J]. J Dent Res,2013,92(2):114-121.
[4] Smith A, Teknos TN, Pan Q. Epithelial to mesenchymal transition in head and neck squamous cell carcinoma[J]. Oral Oncol,2013,49(4):287-292.
[5] Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer[J]. Oral Oncol,2009,45(4-5):309-316.
[6] Pillai R S. MicroRNA function: Multiple mechanisms for a tiny RNA?[J]. RNA,2005,11(12):1753-1761.
[7] Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?[J]. Nat Rev Genet,2008,9(2):102-114.
[8] Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction[J]. Nat Rev Mol Cell Biol,2010,11(3):264-275.
[9] Liu X, Wang A, Heidbreder CE, et al. MicroRNA-24 targeting RNA-binding protein DND1 in tongue squamous cell carcinoma[J]. FEBS Lett,2010,584(18):4115-4120.
[10] Lu YC, Chang JT, Liao CT, et al. OncomiR-196 promotes an invasive phenotype in oral cancer through the NME4-JNK-TIMP1-MMP signaling pathway[J]. Mol Cancer,2014,13(1):218.
[11] Chang CJ, Hsu CC, Chang CH, et al. Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer[J]. Oncol Rep,2011,26(4):1003-1010.
[12] Kim J, Park S, Lee SA, et al. MicroRNA-205 suppresses the oral carcinoma oncogenic activity via down-regulation of Axin-2 in KB human oral cancer cell[J]. Mol Cell Biochem,2014,387(1-2):71-79.
[13] Momen-Heravi F, Trachtenberg AJ, Kuo WP, et al. Genomewide study of salivary microRNAs for detection of oral cancer[J]. J Dent Res,2014,93(7 Suppl):86S-93S.
[14] Chen H, Shalom-Feuerstein R, Riley J, et al. miR-7 and miR-214 are specifically expressed during neuroblastoma differentiation, cortical development and embryonic stem cells differentiation, and control neurite outgrowth in vitro [J]. Biochem Biophys Res Commun,2010,394(4):921-927.
[15] Van Balkom BWM, De Jong OG, Smits M, et al. Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells[J]. Blood,2013,121(19):3997-4006.
[16] Penna E, Orso F, Taverna D. miR-214 as a key hub that controls cancer networks: small player, multiple functions[J]. J Clin Investig Dermatol,2015,135(4):960-969.
[17] Fabian MR, Sonenberg N. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC[J]. Nat Struct Mol Biol,2012,19(6):586-593.
[18] Liu M, Wang J, Huang H, et al. miR-181a-Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma[J]. Biochem Biophys Res Commun,2013,441(2):364-370.
[19] Wang J, Huang H, Wang C, et al. MicroRNA-375 sensitizes tumour necrosis factor-alpha (TNF-α)-induced apoptosis in head and neck squamous cell carcinoma in vitro [J]. Int J Oral Maxillofac Surg,2013,42(8):949-955.
[20] Liu X, Wang C, Chen Z, et al. MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines[J]. Biochem J,2011,440(1):23-31.
[21] Jin Y, Wang C, Liu X, et al. Molecular Characterization of the microRNA-138-Fos-like antigen 1 (FOSL1) regulatory module in squamous cell carcinoma[J]. J Biol Chem,2011,286(46):40104-40109.
[22] Li J, Huang H, Sun L, et al. MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor[J]. Clin Cancer Res,2009,15(12):3998-4008.
[23] Flynt AS, Li N, Thatcher EJ, et al. Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate[J]. Nat Genet,2007,39(2):259-263.
[24] Zhang Z, Li Y, Wang H, et al. Knockdown of miR-214 promotes apoptosis and inhibits cell proliferation in nasopharyngeal carcinoma[J]. PLoS One,2014,9(1):e86149.
[25] Yang H, Kong W, He L, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN[J]. Cancer Res,2008,68(2):425-433.
[26] Penna E, Orso F, Cimino D, et al. microRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C[J]. EMBO J,2011,30(10):1990-2007.
[27] Derfoul A, Juan AH, Difilippantonio MJ, et al. Decreased microRNA-214 levels in breast cancer cells coincides with increased cell proliferation, invasion and accumulation of the Polycomb Ezh2 methyltransferase[J]. Carcinogen,2011,32(11):1607-1614.
[28] Wang Y, Shi D, Chen X, et al. Clinicopathological significance of microRNA-214 in gastric cancer and its effect on cell biological behaviour[J]. PLoS One,2014,9(3):e91307.
[29] Huang S, Yuan Y, Zhuang C, et al. MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinoma[J]. Mol Cancer,2012,11(1):51.
[30] Wang J, Li J, Wang X, et al. Downregulation of microRNA-214 and overexpression of FGFR-1 contribute to hepatocellular carcinoma metastasis[J]. Biochem Biophys Res Commun,2013,439(1):47-53.
[31] Wang X, Chen J, Li F, et al. MiR-214 inhibits cell growth in hepatocellular carcinoma through suppression of β-catenin[J]. Biochem Biophys Res Commun,2012,428(4):525-531.
[32] Shih T, Tien Y, Wen C, et al. MicroRNA-214 downregulation contributes to tumor angiogenesis by inducing secretion of the hepatoma-derived growth factor in human hepatoma[J]. J Hepatol,2012,57(3):584-597.
[33] Scapoli L, Palmieri A, Lo Muzio L, et al. MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression[J]. Int J Immunopathol Pharmacol,2010,23(4):1229-1234.
[34] Yoon AJ, Wang S, Shen J, et al. Prognostic value of miR-375 and miR-214-3p in early stage oral squamous cell carcinoma[J]. Am J Transl Res,2014,6(5):580-592.
[35] Yu Z, Zhong L, 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.

miR-214在口腔鳞状细胞癌中的表达及功能研究

Expression and functional role of miR-214 in oral squamous cell carcinoma

RichHTML

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

[1]	刘恒, 段晓峰. 铁自噬及相关基因NCOA4、FTH1在口腔鳞癌中的研究进展[J]. 中国口腔颌面外科杂志, 2023, 21(1): 87-91.
[2]	季萍萍, 李莉, 吴奕帆, 侯黎莉. 经皮穴位电刺激防治口腔鳞癌患者诱导化疗后骨髓抑制的效果观察[J]. 中国口腔颌面外科杂志, 2022, 20(5): 455-460.
[3]	许刚, 宋其义, 蒋卫东, 刘景秀. 水通道蛋白3在口腔鳞癌中的表达及临床意义[J]. 中国口腔颌面外科杂志, 2022, 20(5): 478-482.
[4]	赵小妹, 夏荣辉, 钟来平, 朱东旺, 张志愿. Nrf2对口腔鳞癌患者TPF诱导化疗效果的影响[J]. 中国口腔颌面外科杂志, 2022, 20(4): 366-370.
[5]	张益益, 杨玥怡, 琚梧桐, 钟来平. 局部晚期口腔鳞癌新辅助免疫靶向治疗2例及文献复习[J]. 中国口腔颌面外科杂志, 2022, 20(4): 413-416.
[6]	魏东亮, 李智, 鞠侯雨, 吴云腾, 郭伟, 任国欣. EGFR靶向药物对口腔癌疼痛缓解作用的机制探讨[J]. 中国口腔颌面外科杂志, 2022, 20(3): 219-224.
[7]	孙大为, 张云, 朱勇. shRNA干扰Rce1基因表达对口腔鳞癌细胞放射敏感性的影响[J]. 中国口腔颌面外科杂志, 2022, 20(2): 123-128.
[8]	努尔曼古丽·牙森, 多力昆·吾甫尔, 白尔娜·吾守尔, 闫广鹏. 血清IL-6、IL-17、TNF-α和IFN-γ水平与60例口腔鳞癌患者临床特征关系探讨[J]. 中国口腔颌面外科杂志, 2022, 20(2): 141-145.
[9]	瞿楚翔, 孙树洋, 张志愿. 从遗传异质性认识口腔鳞癌的侵袭过程[J]. 中国口腔颌面外科杂志, 2022, 20(2): 193-197.
[10]	王育新, 王志勇, 王永功, 王慧明, 王丽珍, 田皞, 叶金海, 付坤, 阮敏, 孙长伏, 孙国文, 刘法昱, 许碧云, 后军, 刘冰, 刘亮, 陈永锋, 陈占伟, 肖灿, 李思毅, 李志勇, 李勇, 李楠, 张陈平, 张东升, 张胜, 张凯, 杨溪, 何巍, 苏彤, 季彤, 林李嵩, 罗瑞华, 赵志立, 胡勤刚, 唐瞻贵, 徐蔚嘉, 黄志权, 黄晓峰, 梁玉洁, 韩正学, 韩伟, 蒋灿华, 喻建军, 蔡志刚, 廖贵清, 廖圣恺, 蔡惠明, 魏建华. 吲哚菁绿荧光成像技术在口腔鳞癌治疗中的应用：中国专家共识[J]. 中国口腔颌面外科杂志, 2022, 20(1): 1-6.
[11]	李行, 许飞虎, 杨云博, 韩楠男, 阮敏. 口腔鳞癌腮腺淋巴结转移的临床病理特征与预后分析[J]. 中国口腔颌面外科杂志, 2022, 20(1): 28-31.
[12]	杨云博, 王钰璞, 李行, 韩楠男, 严明, 阮敏. 半胱氨酸酶抑制剂A在口腔鳞癌中的表达及临床意义[J]. 中国口腔颌面外科杂志, 2021, 19(6): 494-499.
[13]	黄金云, 张心怡, 鞠侯雨, 冀洪海, 任国欣. 口腔微生物稳态与口腔鳞癌患者顺铂敏感性的相关性分析[J]. 中国口腔颌面外科杂志, 2021, 19(6): 500-505.
[14]	黄金云, 张心怡, 鞠侯雨, 冀洪海, 任国欣. 口腔微生物稳态与口腔鳞癌患者顺铂敏感性的相关性分析[J]. 中国口腔颌面外科杂志, 2021, 19(6): 506-510.
[15]	李曼容, 娄雅静. Orem自理模式在90例口腔鳞癌患者游离组织瓣移植术后的应用价值评价[J]. 中国口腔颌面外科杂志, 2021, 19(6): 553-556.