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长链非编码RNA HCP5通过miR-216a-5p/CDC42轴增强宫颈癌的增殖和迁移。

LncRNA HCP5 enhances the proliferation and migration of cervical cancer via miR-216a-5p/CDC42 axis.

作者信息

Li Xiaomin, Chen Bingxin, Huang Anni, Ren Ci, Wang Liming, Zhu Tong, Xiong Jinfeng, Ding Wencheng, Wang Hui

机构信息

Department of Gynecologic Oncology Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Obstetrics and Gynecology Department, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China.

出版信息

J Cancer. 2022 Mar 21;13(6):1882-1894. doi: 10.7150/jca.64730. eCollection 2022.

Abstract

To investigate the important roles of the cancer-promoting long non-coding RNAs (lncRNAs) in cervical cancer, the up-regulated lncRNAs and prognostic analysis were identified through Lnc2Cancer and Lncar. LncRNA-regulated miRNA and miRNA-target mRNA were analyzed based on starBase v2.0 and miTarbase to predict the lncRNA-miRNA-mRNA ceRNA network. Based on the above findings, the abnormally expressed histocompatibility leukocyte antigen complex P5 (HCP5) was identified in 31 cervical cancer patients through RT-qPCR. The stable cell lines were constructed to explore the effect of HCP5 on the promotion of cervical cancer and the regulatory role on the expression of miR-216a-5p and CDC42. Cell Counting Kit-8 (CCK8) assay, cell clone formation, and transwell assay were used to examine proliferation and migration ability of cervical cancer cells. The results displayed that the overexpression of HCP5 promoted cervical cancer cell proliferation and migration , and the elevated HCP5 can also promote tumor growth . Besides, RT-qPCR and western blot assay revealed that elevated HCP5 suppressed miR-216a-5p expression and then up-regulated the expression of CDC42. In contrast, knocking down HCP5 resulted in increased expression of miR-216a-5p and then downregulated the expression of CDC42. Rescue experiments also demonstrated that miR-216a-5p could in part intercept in promotion impact caused by HCP5 on cervical cancer cells. Above all, HCP5, as an oncogene, can promote proliferation and migration ability of cervical cancer via the regulation of the miR-216a-5p/CDC42 axis.

摘要

为了研究促癌长链非编码RNA(lncRNA)在宫颈癌中的重要作用,通过Lnc2Cancer和Lncar鉴定上调的lncRNA并进行预后分析。基于starBase v2.0和miTarbase分析lncRNA调控的miRNA和miRNA靶向的mRNA,以预测lncRNA-miRNA-mRNA竞争性内源RNA(ceRNA)网络。基于上述发现,通过RT-qPCR在31例宫颈癌患者中鉴定出异常表达的组织相容性白细胞抗原复合体P5(HCP5)。构建稳定细胞系,以探讨HCP5对宫颈癌的促进作用以及对miR-216a-5p和CDC42表达的调控作用。采用细胞计数试剂盒-8(CCK8)检测、细胞克隆形成实验和Transwell实验检测宫颈癌细胞的增殖和迁移能力。结果显示,HCP5的过表达促进宫颈癌细胞增殖和迁移,HCP5升高也可促进肿瘤生长。此外,RT-qPCR和蛋白质免疫印迹实验显示,HCP5升高抑制miR-216a-5p表达,进而上调CDC42的表达。相反,敲低HCP5导致miR-216a-5p表达增加,进而下调CDC42的表达。挽救实验还表明,miR-216a-5p可部分阻断HCP5对宫颈癌细胞的促进作用。综上所述,HCP5作为一种癌基因,可通过调控miR-216a-5p/CDC42轴促进宫颈癌的增殖和迁移能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/8990426/6c6785f6e6a7/jcav13p1882g001.jpg

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