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长链非编码RNA ZFAS1通过竞争性结合miR-135a-5p参与前列腺癌细胞的增殖、侵袭和转移。

lncRNA ZFAS1 Is Involved in the Proliferation, Invasion and Metastasis of Prostate Cancer Cells Through Competitively Binding to miR-135a-5p.

作者信息

Pan Jiaqiang, Xu Xingyan, Wang Guangliang

机构信息

Department of Urology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China.

Department of Ophthalmology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Feb 13;12:1135-1149. doi: 10.2147/CMAR.S237439. eCollection 2020.

DOI:10.2147/CMAR.S237439
PMID:32104094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7025677/
Abstract

BACKGROUND

Prostate cancer (PCa) is a common malignant tumor in men. lncRNA ZFAS1 plays a carcinogenic role in many types of cancer; however, its potential role in PCa remains unclear. The current study aimed to determine the expression and function of ZFAS1 in PC.

METHODS

The ZFAS1 expression in PC tissues and cells was determined by quantitative polymerase chain reaction (qPCR). SiZFAS1, miR-135a-5p mimic and miR-135a-5p inhibitor were transfected into PCa cells. The direct target of ZFAS1 was predicted by Starbase and verified by dual-luciferase reporter. Cell viability, proliferation, apoptosis, migration and invasion of the PCa cells were determined by cell counting kit-8, clone formation assay, flow cytometer, scratch and Transwell assay, respectively. The expression levels of related proteins and mRNAs were determined by Western blotting and qPCR.

RESULTS

ZFAS1 expression was up-regulated in PCa cells and tissues. ZFAS1 could competitively bind to miR-135a-5p in PCa cells, and down-regulation of ZFAS1 inhibited cell viability, proliferation, migration, invasion of PCa cells and the occurrence of epithelial-mesenchymal transformation (EMT) and promoted apoptosis of PCa cells and increased the miR-135a-5p expression. Moreover, the function of miR-135a-5p mimic in PCa cells was consistent with ZFAS1 knockdown, while the function of miR-135a-5p inhibitor was opposite to that of miR-135a-5p mimic in PCa cells. The results showed that knocking down ZFAS1 could attenuate the effects of miR-135a-5p inhibitor on cell proliferation, invasion and EMT of PCa cells.

CONCLUSION

Knocking down ZFAS1 could inhibit the proliferation, invasion and metastasis of PCa cells through regulating miR-135a-5p expression.

摘要

背景

前列腺癌(PCa)是男性常见的恶性肿瘤。长链非编码RNA ZFAS1在多种癌症中发挥致癌作用;然而,其在前列腺癌中的潜在作用仍不清楚。本研究旨在确定ZFAS1在前列腺癌中的表达及功能。

方法

采用定量聚合酶链反应(qPCR)检测前列腺癌组织和细胞中ZFAS1的表达。将SiZFAS1、miR-135a-5p模拟物和miR-135a-5p抑制剂转染至前列腺癌细胞中。通过Starbase预测ZFAS1的直接靶点,并通过双荧光素酶报告基因进行验证。分别采用细胞计数试剂盒-8、克隆形成实验、流式细胞仪、划痕实验和Transwell实验检测前列腺癌细胞的活力、增殖、凋亡、迁移和侵袭能力。通过蛋白质免疫印迹法和qPCR检测相关蛋白和mRNA的表达水平。

结果

ZFAS1在前列腺癌细胞和组织中表达上调。ZFAS1可在前列腺癌细胞中与miR-135a-5p竞争性结合,下调ZFAS1可抑制前列腺癌细胞的活力、增殖、迁移、侵袭以及上皮-间质转化(EMT)的发生,并促进前列腺癌细胞凋亡,增加miR-135a-5p的表达。此外,miR-135a-5p模拟物在前列腺癌细胞中的功能与敲低ZFAS1一致,而miR-135a-5p抑制剂在前列腺癌细胞中的功能与miR-135a-5p模拟物相反。结果表明,敲低ZFAS1可减弱miR-135a-5p抑制剂对前列腺癌细胞增殖、侵袭和EMT的影响。

结论

敲低ZFAS1可通过调节miR-135a-5p的表达抑制前列腺癌细胞的增殖、侵袭和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/2bb3460a7269/CMAR-12-1135-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/aa2bbda53e9d/CMAR-12-1135-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/e9b73b80182e/CMAR-12-1135-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/ba7a0817a6cb/CMAR-12-1135-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/737f3c6e56df/CMAR-12-1135-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/a934efa27a55/CMAR-12-1135-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/95d6ae51d62a/CMAR-12-1135-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/2bb3460a7269/CMAR-12-1135-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/aa2bbda53e9d/CMAR-12-1135-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/e9b73b80182e/CMAR-12-1135-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/ba7a0817a6cb/CMAR-12-1135-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/737f3c6e56df/CMAR-12-1135-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/a934efa27a55/CMAR-12-1135-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/95d6ae51d62a/CMAR-12-1135-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63bc/7025677/2bb3460a7269/CMAR-12-1135-g0007.jpg

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