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长链非编码RNA PDIA3P与miR-185-5p相互作用,通过靶向细胞周期蛋白D2调节口腔鳞状细胞癌的进展。

The lncRNA PDIA3P Interacts with miR-185-5p to Modulate Oral Squamous Cell Carcinoma Progression by Targeting Cyclin D2.

作者信息

Sun Cheng-Cao, Zhang Ling, Li Guang, Li Shu-Jun, Chen Zhen-Long, Fu Yun-Feng, Gong Feng-Yun, Bai Tao, Zhang Ding-Yu, Wu Qing-Ming, Li De-Jia

机构信息

Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, China; School of Public Health, Wuhan University of Science and Technology, Wuhan 430065, China.

School of Public Health, Wuhan University of Science and Technology, Wuhan 430065, China.

出版信息

Mol Ther Nucleic Acids. 2017 Dec 15;9:100-110. doi: 10.1016/j.omtn.2017.08.015. Epub 2017 Sep 21.

Abstract

Long noncoding RNAs (lncRNAs) are emerging as important regulators during tumorigenesis by serving as competing endogenous RNAs (ceRNAs). In this study, the qRT-PCR results indicated that the lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) was overexpressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. CCK-8 and clonal colony formation assays were used to detect the effects of PDIA3P on proliferation. Results revealed that silencing PDIA3P by small interfering RNA (siRNA) inhibited OSCC cell proliferation and repressed tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Furthermore, the interaction between PDIA3P and miRNAs was then analyzed by qRT-PCR and luciferase reporter gene assay. We found that PDIA3P negatively regulated miR-185-5p in OSCC cells. Simultaneously, we found that silencing PDIA3P by siRNA suppressed proliferation via miR-185-5p in OSCC cells. Moreover, silencing PDIA3P by siRNA inhibited CCND2 protein (no influence on mRNA levels) expression via miR-185-5p in OSCC cells, and CCND2 facilitated cell proliferation of SCC4 and SCC15 cells induced by sh-PDIA3P#1. Therefore, our study demonstrated that PDIA3P may be a therapeutic target for the treatment of OSCC.

摘要

长链非编码RNA(lncRNA)作为竞争性内源性RNA(ceRNA),在肿瘤发生过程中逐渐成为重要的调节因子。在本研究中,qRT-PCR结果表明,lncRNA蛋白二硫键异构酶家族A成员3假基因1(PDIA3P)在口腔鳞状细胞癌(OSCC)中过表达,并降低了OSCC患者的生存率。采用CCK-8和克隆集落形成试验检测PDIA3P对增殖的影响。结果显示,通过小干扰RNA(siRNA)沉默PDIA3P可抑制OSCC细胞增殖,抑制肿瘤生长,并降低体内增殖抗原Ki-67的表达。此外,通过qRT-PCR和荧光素酶报告基因试验分析了PDIA3P与miRNA之间的相互作用。我们发现PDIA3P在OSCC细胞中负向调节miR-185-5p。同时,我们发现通过siRNA沉默PDIA3P可通过miR-185-5p抑制OSCC细胞的增殖。此外,通过siRNA沉默PDIA3P可通过miR-185-5p抑制OSCC细胞中CCND2蛋白(对mRNA水平无影响)的表达,并且CCND2促进了sh-PDIA3P#1诱导的SCC4和SCC15细胞的增殖。因此,我们的研究表明PDIA3P可能是治疗OSCC的一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/385a/5626923/f2d229c39d31/gr1.jpg

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