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长链非编码RNA LINC00261通过上调GATA6介导的DKK3来抑制前列腺癌的肿瘤发生。

Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3.

作者信息

Li Yang, Li Hai, Wei Xin

机构信息

Department of Urology, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, 130033 Jilin People's Republic of China.

出版信息

Cancer Cell Int. 2020 Sep 30;20:474. doi: 10.1186/s12935-020-01484-5. eCollection 2020.

DOI:10.1186/s12935-020-01484-5
PMID:33013201
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7526381/
Abstract

BACKGROUND

Prostate cancer is one of the leading causes of cancer death in males. Recent studies have reported aberrant expression of lncRNAs in prostate cancer. This study explores the role of LINC00261 in prostate cancer progression.

METHODS

The differentially expressed genes, transcription factors, and lncRNAs related to prostate cancer were predicted by bioinformatics analysis. Prostate cancer tissue samples and cell lines were collected for the determination of the expression of LINC00261 by reverse transcription quantitative polymerase chain reaction. The binding capacity of LINC00261 to the transcription factor GATA6 was detected by RIP, and GATA6 binding to the DKK3 promoter region was assessed by ChIP. In addition, luciferase reporter system was used to verify whether LINC00261 was present at the DKK3 promoter. After gain- and loss-of function approaches, the effect of LINC00261 on prostate cancer in vitro and in vivo was assessed by the determination of cell proliferation, invasion and migration as well as angiogenesis.

RESULTS

LINC00261, GATA6, and DKK3 were poorly expressed in prostate cancer. LINC00261 could inhibit transcriptional expression of DKK3 by recruiting GATA6. Overexpression of LINC00261 inhibited prostate cancer cells proliferation, migration, and invasion as well as angiogenesis, which could be reversed by silencing DKK3. Furthermore, LINC00261 could also suppress the tumorigenicity of cancer cells in vivo.

CONCLUSIONS

Our study demonstrates the inhibitory role of LINC00261 in prostate cancer progression, providing a novel biomarker for early detection of prostate cancer.

摘要

背景

前列腺癌是男性癌症死亡的主要原因之一。最近的研究报道了lncRNAs在前列腺癌中的异常表达。本研究探讨了LINC00261在前列腺癌进展中的作用。

方法

通过生物信息学分析预测与前列腺癌相关的差异表达基因、转录因子和lncRNAs。收集前列腺癌组织样本和细胞系,采用逆转录定量聚合酶链反应测定LINC00261的表达。通过RIP检测LINC00261与转录因子GATA6的结合能力,通过ChIP评估GATA6与DKK3启动子区域的结合。此外,使用荧光素酶报告系统验证LINC00261是否存在于DKK3启动子处。在进行功能获得和功能缺失实验后,通过测定细胞增殖、侵袭、迁移以及血管生成来评估LINC00261对前列腺癌体内外的影响。

结果

LINC00261、GATA6和DKK3在前列腺癌中表达较低。LINC00261可通过招募GATA6抑制DKK3的转录表达。LINC00261的过表达抑制了前列腺癌细胞的增殖、迁移、侵袭以及血管生成,沉默DKK3可逆转这些作用。此外,LINC00261还可在体内抑制癌细胞的致瘤性。

结论

我们的研究证明了LINC00261在前列腺癌进展中的抑制作用,为前列腺癌的早期检测提供了一种新的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/a10a6eba4204/12935_2020_1484_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/d57a58a737e7/12935_2020_1484_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/dd3a3d4e5ba3/12935_2020_1484_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/878b84de2ae4/12935_2020_1484_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/e778be70d382/12935_2020_1484_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/4490d5588c4d/12935_2020_1484_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/84301afaa324/12935_2020_1484_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/a10a6eba4204/12935_2020_1484_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/d57a58a737e7/12935_2020_1484_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/dd3a3d4e5ba3/12935_2020_1484_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/878b84de2ae4/12935_2020_1484_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/e778be70d382/12935_2020_1484_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/4490d5588c4d/12935_2020_1484_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/84301afaa324/12935_2020_1484_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3547/7526381/a10a6eba4204/12935_2020_1484_Fig7_HTML.jpg

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