新疆南部维吾尔族宫颈鳞癌microRNA研究

Investigation of microRNA expression on Uygur cervical squamous cell carcinoma in southern Xinjiang

背景与目的:宫颈癌是新疆地区尤其是新疆南部维吾尔族高发肿瘤,发病机制尚不清楚。微小RNA(microRNA,miRNA)是一类具有重要调控作用的非编码小分子RNA,其表达及功能失调与肿瘤的发生、发展密切相关。本研究筛选并初步研究新疆南部维吾尔族宫颈鳞癌差异表达的miRNA,预测并分析靶基因功能。方法:采用miRNA微阵列芯片技术对5例人乳头瘤病毒(human papillomavirus,HPV)16阳性的新疆南部维吾尔族宫颈鳞癌进行miRNA筛选,应用实时定量RT-PCR方法对筛选出差异表达的miRNA进行初步验证,并检测及分析在83例宫颈癌中的表达结果,应用targetscan、miRwalk、miRanda及Pictar四种软件预测其靶基因。结果:新疆南部维吾尔族HPV16阳性宫颈鳞癌差异表达基因18个,对差异表达显著的miRNA-138和miRNA-720进行了初步验证并预测靶基因,预测两者共同的靶基因是EZH2;与40例正常对照相比,miRNA-138、miRNA-720在83例宫颈鳞癌组织中均表达下调(P<0.05);下调的miRNA-138、miRNA-720与淋巴结转移、脉管浸润有关(P<0.05),但与年龄、宫颈壁累及范围及HPV16感染无明显关系(P>0.05);miRNA-720与临床分期、肿瘤体积有关(P<0.05)。结论:miRNA-138、miRNA-720在新疆南部维吾尔族宫颈鳞癌组织中均表达下调,两者共同的靶基因是EZH2,可能与宫颈癌的侵润和转移有关。

Background and purpose：Cervical cancer is one of the most common cancer in Xinjiang, especially for Uygur from southern Xinjiang and its pathogenesis is not clear. MicroRNA （miRNA） is a class of small non-coding RNA playing an important regulatory role. Its expression and dysfunction is closely related to the development of tumors. In this study, we screen and preliminary analyse expression of miRNA in cervical squamous cell carcinoma samples with human papillomavirus （HPV） 16 positive of Uygur patients. The target genes of miRNA were predicted.Methods：miRNAs were pre-screened by using miRNA microarray technology in 5 cases of HPV16 positivity Uygur patients from southern Xinjiang with cervical squamous cell carcinoma. Fifteen cases specimens were examined by qRT-PCR for preliminary veriifcation, and 83 cases of cervical cancer were detected and analysed the expression of miRNA; Targeted genes were predicted by using four softwares of target scan, miRwalk, miRanda and Pictar.Results：Eighteen differentially expressed miRNAs were selected by SAM software in 5 cases of HPV16 positivity southern Xinjiang Uygur cases with cervical squamous cell carcinoma.miRNA-138 and miRNA-720 were found expressed signiifcantly different by initial veriifcation. Contrasted with 40 normal cases, miR-138 and miR-720 were down-regulated in 83 Uygur patients from southern Xinjiang with cervical squamous cell carcinoma （P〈0.05）,and correlated with lymph node matastasis and vascular invasion （P〈0.05）, no correlation with age and the range of cervical wall involvement and HPV16 （P〉0.05）. miRNA-720 was correlated with clinical stage and tumor size （P〈0.05）; And the commonly targeted gene between miRNA-138 and miRNA-720 was EZH2.Conclusion：miRNA-138 and miRNA-720 were downregulated in Uygur patients from southern Xinjiang with cervical squamous cell carcinoma, and the common target gene was EZH2.The expression of miR-720 and miR-138 were correlated with relevant risk factors of invasion and metastasis.