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SPOCK2的上调通过调节MT1-MMP/MMP2途径抑制前列腺癌细胞的侵袭和迁移。

Upregulation of SPOCK2 inhibits the invasion and migration of prostate cancer cells by regulating the MT1-MMP/MMP2 pathway.

作者信息

Liu Gang, Ren Fang, Song Yongsheng

机构信息

Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

PeerJ. 2019 Jul 12;7:e7163. doi: 10.7717/peerj.7163. eCollection 2019.

DOI:10.7717/peerj.7163
PMID:31338255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6628882/
Abstract

BACKGROUND

It is known that secreted protein acidic and cysteine rich (osteonectin), cwcv and kazal-like domains proteoglycan 2 (SPOCK2) plays a significant role in the development and progression of several human cancers; however, the role of SPOCK2 in prostate cancer (PCa) remains unclear. This study aimed to find the role and mechanism of SPOCK2 in the development and progression of PCa.

METHODS

The messenger ribonucleic acid (mRNA) expression of in PCa tissue was detected by real-time polymerase chain reaction (PCR). Upregulation of the gene was achieved using the DU145 and LNCaP cells by transfecting the cells with recombinant fragment. Cell invasion and migration ability were detected by transwell chamber and wound healing assay. The expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase 2 (MMP2) in the cells was detected by Western Blot and zymography gel assay.

RESULTS

The mRNA level of was significantly lower in the PCa tissue compared to benign prostate hyperplasia. Upregulation of inhibited cell invasion and migration in DU145 and LNCaP cells, inhibited the expression of MT1-MMP and MMP2 and, inhibited activation of MMP2 in DU145 and LNCaP cells.

CONCLUSION

SPOCK2 is associated with the progression of PCa. Upregulation of SPOCK2 can inhibit PCa cell invasion and metastasis by decreasing MT1-MMP and MMP2 gene expression and decreasing MMP2 protein activation.

摘要

背景

已知富含酸性和半胱氨酸的分泌蛋白(骨连接蛋白)、cwcv和类kazal结构域蛋白聚糖2(SPOCK2)在多种人类癌症的发生和发展中起重要作用;然而,SPOCK2在前列腺癌(PCa)中的作用仍不清楚。本研究旨在探讨SPOCK2在PCa发生和发展中的作用及机制。

方法

采用实时聚合酶链反应(PCR)检测PCa组织中信使核糖核酸(mRNA)的表达。通过用重组片段转染DU145和LNCaP细胞来上调该基因。采用Transwell小室和伤口愈合试验检测细胞侵袭和迁移能力。通过蛋白质免疫印迹法和酶谱凝胶分析检测细胞中膜型1基质金属蛋白酶(MT1-MMP)和基质金属蛋白酶2(MMP2)的表达。

结果

与良性前列腺增生相比,PCa组织中该基因的mRNA水平显著降低。上调该基因可抑制DU145和LNCaP细胞的侵袭和迁移,抑制MT1-MMP和MMP2的表达,并抑制DU145和LNCaP细胞中MMP2的激活。

结论

SPOCK2与PCa的进展有关。上调SPOCK2可通过降低MT1-MMP和MMP2基因表达以及降低MMP2蛋白激活来抑制PCa细胞的侵袭和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/b40af0d4163f/peerj-07-7163-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/297af098339b/peerj-07-7163-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/6f09d844996a/peerj-07-7163-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/fd4c6ab9c32d/peerj-07-7163-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/7bf048d94064/peerj-07-7163-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/354aeb43b055/peerj-07-7163-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/b40af0d4163f/peerj-07-7163-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/297af098339b/peerj-07-7163-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/6f09d844996a/peerj-07-7163-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/fd4c6ab9c32d/peerj-07-7163-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/7bf048d94064/peerj-07-7163-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/354aeb43b055/peerj-07-7163-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6628882/b40af0d4163f/peerj-07-7163-g006.jpg

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