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长链非编码RNA通过作为微小RNA-511-3p的分子海绵发挥作用,从而增加FGFR2表达,增强宫颈癌的恶性程度。

Long Noncoding RNA Enhances the Malignancy of Cervical Cancer by Functioning as a Molecular Sponge of microRNA-511-3p and Consequently Increasing FGFR2 Expression.

作者信息

Dai Jun, Wei Rujia, Zhang Peihai, Liu Peishu

机构信息

Department of Gynaecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People's Republic of China.

School of Life Sciences, Liaocheng University, Liaocheng, Shandong 252004, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Jan 23;12:567-580. doi: 10.2147/CMAR.S238373. eCollection 2020.

DOI:10.2147/CMAR.S238373
PMID:32158261
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6986931/
Abstract

PURPOSE

A long noncoding RNA called ZFPM2 antisense RNA 1 () has been verified as a key modulator in multiple human cancer types. Nonetheless, the expression and functions of in cervical cancer remain poorly understood. Therefore, our purpose was to characterize the expression pattern, clinical value, and detailed roles of in cervical cancer.

METHODS

Reverse-transcription quantitative PCR was carried out to measure expression in cervical cancer. A Cell Counting Kit-8 assay, flow cytometry, Transwell migration and invasion assays, and a tumor xenograft experiment were conducted to determine the influence of on cervical cancer cell proliferation, apoptosis, migration, and invasion in vitro and on tumor growth in vivo, respectively.

RESULTS

was found to be aberrantly upregulated in cervical cancer, and its upregulation was associated with unfavorable values of clinical parameters. A knockdown significantly reduced cervical cancer cell proliferation, migration, and invasion and increased apoptosis in vitro. The knockdown decelerated tumor growth of cervical cancer cells in vivo. Molecular investigation indicated that acts as a molecular sponge of microRNA-511-3p (miR-511-3p) in cervical cancer cells. Fibroblast growth factor receptor 2 () mRNA was validated as a direct target of miR-511-3p in cervical cancer, and its expression was positively modulated by . The effects of the knockdown on malignant characteristics of cervical cancer cells were greatly attenuated by miR-511-3p inhibition.

CONCLUSION

promotes cervical cancer progression through upregulation of miR-511-3p-FGFR2 axis output, thereby pointing to possible diagnostics and therapeutics based on the -miR-511-3p-FGFR2 pathway.

摘要

目的

一种名为锌指蛋白M2反义RNA 1(ZFPM2-AS1)的长链非编码RNA已被证实是多种人类癌症类型中的关键调节因子。然而,ZFPM2-AS1在宫颈癌中的表达和功能仍知之甚少。因此,我们的目的是明确ZFPM2-AS1在宫颈癌中的表达模式、临床价值及具体作用。

方法

采用逆转录定量PCR检测宫颈癌中ZFPM2-AS1的表达。分别进行细胞计数试剂盒-8检测、流式细胞术、Transwell迁移和侵袭实验以及肿瘤异种移植实验,以确定ZFPM2-AS1对宫颈癌细胞增殖、凋亡、迁移和侵袭的体外影响以及对体内肿瘤生长的影响。

结果

发现ZFPM2-AS1在宫颈癌中异常上调,其上调与临床参数的不良值相关。敲低ZFPM2-AS1可显著降低宫颈癌细胞的增殖、迁移和侵袭,并增加体外细胞凋亡。敲低ZFPM2-AS1可减缓体内宫颈癌细胞的肿瘤生长。分子研究表明,ZFPM2-AS1在宫颈癌细胞中作为微小RNA-511-3p(miR-511-3p)的分子海绵发挥作用。成纤维细胞生长因子受体2(FGFR2)mRNA被证实为宫颈癌中miR-511-3p的直接靶标,其表达受到ZFPM2-AS1的正向调节。抑制miR-511-3p可大大减弱敲低ZFPM2-AS1对宫颈癌细胞恶性特征的影响。

结论

ZFPM2-AS1通过上调miR-511-3p-FGFR2轴输出促进宫颈癌进展,从而为基于ZFPM2-AS1-miR-511-3p-FGFR2途径的诊断和治疗提供了可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/9a270cce7c45/CMAR-12-567-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/cb581e75f09d/CMAR-12-567-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/81d61e0f3442/CMAR-12-567-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/1cf622d54226/CMAR-12-567-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/ce7603b6a5f6/CMAR-12-567-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/07dbf187b35d/CMAR-12-567-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/2dbcd5f9097d/CMAR-12-567-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/9a270cce7c45/CMAR-12-567-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/cb581e75f09d/CMAR-12-567-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/81d61e0f3442/CMAR-12-567-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/1cf622d54226/CMAR-12-567-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/ce7603b6a5f6/CMAR-12-567-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/07dbf187b35d/CMAR-12-567-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/2dbcd5f9097d/CMAR-12-567-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/6986931/9a270cce7c45/CMAR-12-567-g0007.jpg

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