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长链非编码RNA CCHE1通过上调增殖细胞核抗原促进宫颈癌细胞增殖。

Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA.

作者信息

Yang Meng, Zhai Xu, Xia Bairong, Wang Yanying, Lou Ge

机构信息

Department of Gynecology, The Affiliated Tumor Hospital, Harbin Medical University, Baojian Road No. 6, Nangang District, Harbin, 150081, China.

Department of Anesthesia, The Affiliated Tumor Hospital, Harbin Medical University, Baojian Road No. 6, Nangang District, Harbin, 150081, China.

出版信息

Tumour Biol. 2015 Sep;36(10):7615-22. doi: 10.1007/s13277-015-3465-4. Epub 2015 Apr 29.

Abstract

Long noncoding RNAs (lncRNAs) have been shown to play important roles in carcinogenesis and progression. However, the roles and functional mechanisms of lncRNAs in cervical cancer remain largely unknown. In this study, we found that cervical carcinoma high-expressed lncRNA 1 (lncRNA-CCHE1) was significantly upregulated in cervical cancer tissues. The higher expression of CCHE1 was significantly correlated with large tumor size, advanced Federation of Gynecology and Obstetrics stage, uterine corpus invasion, and poor survival. Gain-of-function and loss-of-function experiments demonstrated that CCHE1 overexpression promotes the proliferation of cervical cancer cell. By contrast, the depletion of CCHE1 inhibits the proliferation of cervical cancer cells. RNA pull-down assays confirmed that CCHE1 physically associates with proliferating cell nuclear antigen (PCNA) messenger RNA, consequently enhances the expression of PCNA. The expression of CCHE1 and PCNA is significantly correlated in cervical cancer tissues. The depletion of PCNA abolishes the effects of CCHE1 on the proliferation of cervical cancer cells. Taken together, these findings indicate that CCHE1 plays a pivotal role in cervical cancer cell proliferation via increasing PCNA expression and serves as a potential prognostic biomarker and therapeutic target in human cervical cancer.

摘要

长链非编码RNA(lncRNAs)已被证明在肿瘤发生和进展中发挥重要作用。然而,lncRNAs在宫颈癌中的作用和功能机制仍 largely未知。在本研究中,我们发现宫颈癌高表达lncRNA 1(lncRNA-CCHE1)在宫颈癌组织中显著上调。CCHE1的高表达与肿瘤大尺寸、晚期妇产科联盟分期、子宫体浸润及不良生存显著相关。功能获得和功能丧失实验表明,CCHE1过表达促进宫颈癌细胞增殖。相比之下,CCHE1的缺失抑制宫颈癌细胞增殖。RNA下拉试验证实CCHE1与增殖细胞核抗原(PCNA)信使核糖核酸物理结合,从而增强PCNA的表达。CCHE1和PCNA的表达在宫颈癌组织中显著相关。PCNA的缺失消除了CCHE1对宫颈癌细胞增殖的影响。综上所述,这些发现表明CCHE1通过增加PCNA表达在宫颈癌细胞增殖中起关键作用,并作为人类宫颈癌的潜在预后生物标志物和治疗靶点。

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