Piwil2 modulates the invasion and metastasis of prostate cancer by regulating the expression of matrix metalloproteinase-9 and epithelial-mesenchymal transitions

Yang,Yanfeng; Zhang,Xuepei; Song,Dongkui; Wei,Jinxing

doi:10.3892/ol.2015.3392

Piwil2 modulates the invasion and metastasis of prostate cancer by regulating the expression of matrix metalloproteinase-9 and epithelial-mesenchymal transitions

Authors:
- Yanfeng Yang
- Xuepei Zhang
- Dongkui Song
- Jinxing Wei
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Affiliations: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: June 19, 2015 https://doi.org/10.3892/ol.2015.3392
Pages: 1735-1740

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Abstract

Piwi-like RNA-mediated gene silencing 2 (Piwil2) is an oncogene that is highly expressed in breast, gastric, colorectal and papillary thyroid cancer. As a candidate oncogene, its role in prostrate cancer has yet to be elucidated. In the present study, 30 tumor specimens and four prostate cancer cell lines were analyzed. The total RNA and protein from the specimens and the cells were analyzed using quantitative polymerase chain reaction and western blotting, respectively. The expression of Piwil2 in PC‑3 cells was knocked down using specific small hairpin RNA. Transwell assays and wound‑healing models were used to assess cell invasion and migration. In addition, the expression of several factors associated with epithelial‑mesenchymal transitions (EMT) were evaluated by western blotting. The results revealed that the Piwil2 gene was associated with the Gleason score and the tumor‑node‑metastasis stage of the tumor tissues. Cell invasion and migration decreased significantly in PC‑3 cells with knocked-down Piwil2. In addition, silencing Piwil2 downregulated the expression of N‑cadherin, Twist and vimentin and upregulated the expression of E‑cadherin, factors associated with EMT, and also reduced the expression of matrix metalloproteinase‑9. Piwil2 was demonstrated to possess an important role in the invasive ability of prostate cancer, and therefore, may be a potential therapeutic target for the treatment of this cancer.

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1	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI
2	Beltran H, Beer TM, Carducci MA, et al: New therapies for castration-resistant prostate cancer: efficacy and safety. Eur Urol. 60:279–290. 2011. View Article : Google Scholar : PubMed/NCBI
3	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
4	Chang SS and Kibel AS: The role of systemic cytotoxic therapy for prostate cancer. BJU Int. 103:8–17. 2009. View Article : Google Scholar : PubMed/NCBI
5	Ni J, Cozzi P, Hao J, et al: Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway. Int J Biochem Cell Biol. 45:2736–2748. 2013. View Article : Google Scholar : PubMed/NCBI
6	Lee JH, Schütte D, Wulf G, et al: Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Hum Mol Genet. 15:201–211. 2006. View Article : Google Scholar : PubMed/NCBI
7	Cox DN, Chao A, Baker J, et al: A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev. 12:3715–3727. 1998. View Article : Google Scholar : PubMed/NCBI
8	Sasaki T, Shiohama A, Minoshima S and Shimizu N: Identification of eight members of the Argonaute family in the human genome. Genomics. 82:323–330. 2003. View Article : Google Scholar : PubMed/NCBI
9	Kuramochi-Miyagawa S, Kimura T, Ijiri TW, et al: Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development. 131:839–849. 2004. View Article : Google Scholar : PubMed/NCBI
10	Liu X, Sun Y, Guo J, et al: Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int J Cancer. 118:1922–1929. 2006. View Article : Google Scholar : PubMed/NCBI
11	He G, Chen L, Ye Y, et al: Piwil2 expressed in various stages of cervical neoplasia is a potential complementary marker for p16. Am J Transl Res. 2:156–169. 2010.PubMed/NCBI
12	Liu JJ, Shen R, Chen L, et al: Piwil2 is expressed in various stages of breast cancers and has the potential to be used as a novel biomarker. Int J Clin Exp Pathol. 3:328–337. 2010.PubMed/NCBI
13	Yin DT, Li HQ, Wang YF, et al: Expression of Piwil2 and its relationship with tumor invasion and metastasis in papillary thyroid carcinoma. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 46:237–239. 2011.(In Chinese). PubMed/NCBI
14	Li D, Sun X, Yan D, et al: Piwil2 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity. Exp Biol Med (Maywood). 237:1231–1240. 2012. View Article : Google Scholar : PubMed/NCBI
15	General Assembly of the World Medical Association, . World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. J Am Coll Dent. 81:14–18. 2014.PubMed/NCBI
16	Wang Y, Liu Y, Shen X, et al: The PIWI protein acts as a predictive marker for human gastric cancer. Int J Clin Exp Pathol. 5:315–325. 2012.PubMed/NCBI
17	Oh SJ, Kim SM, Kim YO and Chang HK: Clinicopathologic implications of PIWIL2 expression in colorectal cancer. Korean J Pathol. 46:318–323. 2012. View Article : Google Scholar : PubMed/NCBI
18	Greither T, Koser F, Kappler M, et al: Expression of human Piwi-like genes is associated with prognosis for soft tissue sarcoma patients. BMC Cancer. 12:2722012. View Article : Google Scholar : PubMed/NCBI
19	Shaikhibrahim Z, Lindstrot A, Ochsenfahrt J, Fuchs K and Wernert N: Epigenetics-related genes in prostate cancer: Expression profile in prostate cancer tissues, androgen-sensitive and -insensitive cell lines. Int J Mol Med. 31:21–25. 2013.PubMed/NCBI
20	Bubendorf L, Schöpfer A, Wagner U, et al: Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 31:578–583. 2000. View Article : Google Scholar : PubMed/NCBI
21	Dong Z, Bonfil RD, Chinni S, et al: Matrix metalloproteinase activity and osteoclasts in experimental prostate cancer bone metastasis tissue. Am J Pathol. 166:1173–1186. 2005. View Article : Google Scholar : PubMed/NCBI
22	Boyer B, Vallés AM and Edme N: Induction and regulation of epithelial-mesenchymal transitions. Biochem Pharmacol. 60:1091–1099. 2000. View Article : Google Scholar : PubMed/NCBI