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微小RNA的差异调节与口腔癌相关。

The differential regulation of microRNAs is associated with oral cancer.

作者信息

Tsai Shih-Chang, Huang Sheng-Fong, Chiang Jo-Hua, Chen Yen-Fu, Huang Chia-Chang, Tsai Ming-Hsui, Tsai Fuu-Jen, Kao Ming-Ching, Yang Jai-Sing

机构信息

Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.

Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi County, Taiwan, R.O.C.

出版信息

Oncol Rep. 2017 Sep;38(3):1613-1620. doi: 10.3892/or.2017.5811. Epub 2017 Jul 12.

Abstract

Oral squamous cell carcinoma (OSCC), is the most frequently occurring malignant head and neck tumor, generally it exhibits a poor prognosis, and metastasis is the main cause of death in these cancer patients. The discovery of reliable prognostic indicators for tumors progression would greatly improve clinical treatments. MicroRNAs (miRNAs) play a critical role in the degradation of mRNA and the inhibition of protein synthesis. The miRNAs function either as tumor suppressors or as oncogenes in tumorigenesis, and little is known about the clinical significance of miRNA expression profiles in oral cancers. In the present study, we investigated the expression profiles of miR-375, miR-204 and miR-196a in 39 healthy and tumor tissue pairs of oral cancer patients using TaqMan real-time quantitative polymerase chain reaction (qPCR). The predicted target genes for miR-375, miR-204 and miR-196a were confirmed using luciferase reporter-based assays and western blot analyses. In oral cancer tissue, the expression of miR-375 and miR-204 decreased, whereas the expression of miR-196a was significantly elevated. In OSCC, HOXB8 and p27 (CDKN1B) were the direct target genes of miR-196a, whereas HMGA2 was the direct target gene of miR-204. HOXB8 and p27 (CDKN1B) protein expression levels were inhibited by miR-196a, whereas the protein expression level of HMGA2 was inhibited by miR-204. Furthermore, the miR-196a inhibitor blocked cell proliferation. Our results indicate that the combined expression signatures of miR-375, miR-204 and miR-196a are promising biomarkers for the diagnosis, prognosis and treatment of OSCC.

摘要

口腔鳞状细胞癌(OSCC)是头颈部最常见的恶性肿瘤,其预后通常较差,转移是这些癌症患者死亡的主要原因。发现可靠的肿瘤进展预后指标将大大改善临床治疗。微小RNA(miRNA)在mRNA降解和蛋白质合成抑制中起关键作用。miRNA在肿瘤发生过程中既可以作为肿瘤抑制因子发挥作用,也可以作为癌基因,而关于miRNA表达谱在口腔癌中的临床意义知之甚少。在本研究中,我们使用TaqMan实时定量聚合酶链反应(qPCR)检测了39对口腔癌患者的健康组织和肿瘤组织中miR-375、miR-204和miR-196a的表达谱。使用基于荧光素酶报告基因的检测和蛋白质印迹分析证实了miR-375、miR-204和miR-196a的预测靶基因。在口腔癌组织中,miR-375和miR-204的表达降低,而miR-196a的表达显著升高。在OSCC中,HOXB8和p27(CDKN1B)是miR-196a的直接靶基因,而HMGA2是miR-204的直接靶基因。miR-196a抑制HOXB8和p27(CDKN1B)蛋白表达水平,而miR-204抑制HMGA2蛋白表达水平。此外,miR-196a抑制剂可阻断细胞增殖。我们的结果表明,miR-375、miR-204和miR-196a的联合表达特征有望成为OSCC诊断、预后和治疗的生物标志物。

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