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微小RNA-124下调SOX8表达并抑制非小细胞肺癌中的细胞增殖。

miRNA-124 down-regulates SOX8 expression and suppresses cell proliferation in non-small cell lung cancer.

作者信息

Xie Chao, Han Yunwei, Liu Yi, Han Lei, Liu Jie

机构信息

Department of Oncology, Qilu Hospital, Shandong University Jinan 250000, Shandong, China.

Department of Oncology, Affiliated Hospital of Luzhou Medical College Luzhou 646000, Sichuan, China.

出版信息

Int J Clin Exp Pathol. 2014 Oct 15;7(11):7518-26. eCollection 2014.

Abstract

Non-small lung cell carcinoma (NSCLC) is a leading lethal disease and a global health burden. The function of the Sex determining region Y (SRY)-related high mobility group box (SOX) family gene in cancer has attracted the attention of more and more scientists recently, yet there are few reports regarding the role of SOX in NSCLC. Our study aimed to investigate the expression of SOX8, a protein belonging to the E group of the SOX family, as well as SOX9, in non-small cell lung cancer (NSCLC) and the relationship of gene expression to clinicopathological factors and prognosis in patients. Immunohistochemical analysis was used to measure the expression of SOX8 in 80 NSCLC and 7 adjacent normal tissues. SOX8 expression was detected as elevated in tumor samples and correlated to tumor size (P < 0.001), lymph node metastasis (P = 0.001), differentiation classification (P = 0.015), and clinical stage (P = 0.013) significantly. Moreover, Kaplan-Meier survival analysis demonstrated that shorter survival time for patients who had higher SOX8 expression (P < 0.001). In addition, our experiments indicate that miRNA-124 functions as a tumor suppressor in NSCLC. We also demonstrate miRNA-124 directly targeted and decreased SOX8 in NSCLC cell lines, suggesting smiRNA-124 may regulate NSCLC cell proliferation via decreasing SOX8 (oncogenicity of biomarker in NSCLC).

摘要

非小细胞肺癌(NSCLC)是一种主要的致命疾病,也是全球的健康负担。性别决定区Y(SRY)相关高迁移率族盒(SOX)家族基因在癌症中的作用最近吸引了越来越多科学家的关注,然而关于SOX在NSCLC中的作用的报道却很少。我们的研究旨在调查属于SOX家族E组的蛋白质SOX8以及SOX9在非小细胞肺癌(NSCLC)中的表达,以及基因表达与患者临床病理因素和预后的关系。采用免疫组织化学分析方法检测80例NSCLC组织和7例癌旁正常组织中SOX8的表达。检测发现肿瘤样本中SOX8表达升高,且与肿瘤大小(P < 0.001)、淋巴结转移(P = 0.001)、分化分级(P = 0.015)和临床分期(P = 0.013)显著相关。此外,Kaplan-Meier生存分析表明,SOX8表达较高的患者生存时间较短(P < 0.001)。另外,我们的实验表明miRNA-124在NSCLC中起肿瘤抑制作用。我们还证明miRNA-124在NSCLC细胞系中直接靶向并降低SOX8,提示smiRNA-124可能通过降低SOX8(NSCLC中生物标志物的致癌性)来调节NSCLC细胞增殖。

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