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lncRNA DANCR/miR-138/Sox4的正反馈回路促进非小细胞肺癌的恶性发展。

The positive feedback loop of lncRNA DANCR/miR-138/Sox4 facilitates malignancy in non-small cell lung cancer.

作者信息

Bai Yong, Zhang Guojun, Chu Heying, Li Ping, Li Juan

机构信息

Department of Respiratory, The First Affiliated Hospital of Zhengzhou University China.

出版信息

Am J Cancer Res. 2019 Feb 1;9(2):270-284. eCollection 2019.

Abstract

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide. The abnormal expression of long non-coding RNAs (lncRNAs) has been reported to be closely associated with the progression of human cancers, including NSCLC. Here, we demonstrated that differentiation antagonizing noncoding RNA (DANCR) was overexpressed in NSCLC tissues. Upregulation of DANCR expression was significantly associated with larger tumor size, advanced TNM stage and lymph node metastasis, and also predicted poor prognoses of patients with NSCLC. Functional experiments showed that DANCR enhanced NSCLC growth and metastasis both and . Further investigation revealed that DANCR could compete with the Sox4 mRNA to bind with miR-138, thus affecting Sox4 expression. In addition, we found that Sox4 bound to the promoter regions of gene to activate DANCR expression, suggesting a positive feedback loop of DANCR/miR-138/Sox4 in NSCLC. Taken together, these results provide a comprehensive analysis of the roles of DANCR as a competing endogenous RNA (ceRNA) in NSCLC progression.

摘要

非小细胞肺癌(NSCLC)是全球最常见的癌症之一。据报道,长链非编码RNA(lncRNAs)的异常表达与包括NSCLC在内的人类癌症进展密切相关。在此,我们证明了分化拮抗非编码RNA(DANCR)在NSCLC组织中过表达。DANCR表达上调与更大的肿瘤大小、晚期TNM分期和淋巴结转移显著相关,并且还预示着NSCLC患者的预后不良。功能实验表明,DANCR在体内和体外均增强了NSCLC的生长和转移。进一步研究发现,DANCR可以与Sox4 mRNA竞争结合miR-138,从而影响Sox4表达。此外,我们发现Sox4与DANCR基因的启动子区域结合以激活DANCR表达,提示在NSCLC中存在DANCR/miR-138/Sox4的正反馈环。综上所述,这些结果全面分析了DANCR作为竞争性内源RNA(ceRNA)在NSCLC进展中的作用。

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