MicroRNA‑328 directly targets p21‑activated protein kinase 6 inhibiting prostate cancer proliferation and enhancing docetaxel sensitivity

Liu,Chunhui; Zhang,Lei; Huang,Yeqing; Lu,Kai; Tao,Tao; Chen,Shuqiu; Zhang,Xiaowen; Guan,Han; Chen,Ming; Xu,Bin

doi:10.3892/mmr.2015.4390

MicroRNA‑328 directly targets p21‑activated protein kinase 6 inhibiting prostate cancer proliferation and enhancing docetaxel sensitivity

Authors:
- Chunhui Liu
- Lei Zhang
- Yeqing Huang
- Kai Lu
- Tao Tao
- Shuqiu Chen
- Xiaowen Zhang
- Han Guan
- Ming Chen
- Bin Xu
View Affiliations

Affiliations: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: September 30, 2015 https://doi.org/10.3892/mmr.2015.4390
Pages: 7389-7395
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Prostate cancer (Pca) has one of the highest mortality rates for malignant cancers worldwide. Previous research has demonstrated that numerous genes are aberrantly expressed during Pca onset and development. p21‑activated protein kinase 6 (PAK6) is known to be overexpressed in primary and metastatic Pca, however the mechanism of this aberrant expression remains unknown. In the present study, immunohistochemistry demonstrated that PAK6 is overexpressed in castration‑resistant Pca (CRPC). Furthermore, PAK6 overexpression was regulated by microRNA (miR)‑328. Luciferase reporter assay and western blot analysis indicated that PAK6 was directly targeted by miR‑328. Forced expression of miR‑328 enhanced docetaxel sensitivity, inhibited cell proliferation and promoted cell apoptosis without affecting the cell cycle. This indicates that miR‑328 performs important functions in CRPC progression via PAK6 regulation. This mechanism may be used to enhance the effect of docetaxel.

View Figures

View References

1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Cookson MS, Roth BJ, Dahm P, Engstrom C, Freedland SJ, Hussain M, Lin DW, Lowrance WT, Murad MH, Oh WK, et al: Castration-resistant prostate cancer: AUA Guideline. J Urol. 190:429–438. 2013. View Article : Google Scholar : PubMed/NCBI
3	Willard SS and Koochekpour S: Regulators of gene expression as biomarkers for prostate cancer. Am J Cancer Res. 2:650–657. 2012.
4	Yang F, Li X, Sharma M, Zarnegar M, Lim B and Sun Z: Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6. J Biol Chem. 276:15345–15353. 2001. View Article : Google Scholar : PubMed/NCBI
5	Lee SR, Ramos SM, Ko A, Masiello D, Swanson KD, Lu ML and Balk SP: AR and ER interaction with a p21-activated kinase (PAK6). Mol Endocrinol. 16:85–99. 2002. View Article : Google Scholar : PubMed/NCBI
6	Kaur R, Yuan X, Lu ML and Balk SP: Increased PAK6 expression in prostate cancer and identification of PAK6 associated proteins. Prostate. 68:1510–1516. 2008. View Article : Google Scholar : PubMed/NCBI
7	Schrantz N, da Silva Correia J, Fowler B, Ge Q, Sun Z and Bokoch GM: Mechanism of p21-activated kinase 6-mediated inhibition of androgen receptor signaling. J Biol Chem. 279:1922–1931. 2004. View Article : Google Scholar
8	Wen X, Li X, Liao B, Liu Y, Wu J, Yuan X, Ouyang B, Sun Q and Gao X: Knockdown of p21-activated kinase 6 inhibits prostate cancer growth and enhances chemosensitivity to docetaxel. Urology. 73:1407–1411. 2009. View Article : Google Scholar : PubMed/NCBI
9	Zhang M, Siedow M, Saia G and Chakravarti A: Inhibition of p21-activated kinase 6 (PAK6) increases radiosensitivity of prostate cancer cells. Prostate. 70:807–816. 2010.PubMed/NCBI
10	Ayub SG, Kaul D and Ayub T: Microdissecting the role of microRNAs in the pathogenesis of prostate cancer. Cancer Genet. 208:289–302. 2015. View Article : Google Scholar : PubMed/NCBI
11	Chua JH, Armugam A and Jeyaseelan K: MicroRNAs: Biogenesis, function and applications. Curr Opin Mol Ther. 11:189–199. 2009.PubMed/NCBI
12	Xu B, Niu X, Zhang X, Tao J, Wu D, Wang Z, Li P, Zhang W, Wu H, Feng N, et al: miR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS. Mol Cell Biochem. 350:207–213. 2011. View Article : Google Scholar : PubMed/NCBI
13	Epstein JI, Allsbrook WE Jr, Amin MB and Egevad LL; ISUP Grading Committee: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 29:1228–1242. 2005. View Article : Google Scholar : PubMed/NCBI
14	Feldman BJ and Feldman D: The development of androgen-independent prostate cancer. Nat Rev Cancer. 1:34–45. 2001. View Article : Google Scholar
15	Fang YX and Gao WQ: Roles of microRNAs during prostatic tumorigenesis and tumor progression. Oncogene. 33:135–147. 2014. View Article : Google Scholar
16	McKee TC and Tricoli JV: Epigenetics of prostate cancer. Methods Mol Biol. 1238:217–234. 2015. View Article : Google Scholar
17	Di Leva G, Garofalo M and Croce CM: MicroRNAs in cancer. Annu Rev Pathol. 9:287–314. 2014. View Article : Google Scholar :
18	Deng JH, Deng Q, Kuo CH, Delaney SW and Ying SY: MiRNA targets of prostate cancer. Mol Biol Methods. 936:357–369. 2013. View Article : Google Scholar
19	Clapé C, Fritz V, Henriquet C, Apparailly F, Fernandez PL, Iborra F, Avancès C, Villalba M, Culine S and Fajas L: miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice. PLoS One. 4:e75422009. View Article : Google Scholar : PubMed/NCBI
20	Verdoodt B, Neid M, Vogt M, Kuhn V, Liffers ST, Palisaar RJ, Noldus J, Tannapfel A and Mirmohammadsadegh A: MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer. Int J Oncol. 43:307–314. 2013.PubMed/NCBI
21	Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, et al: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 102:13944–13949. 2005. View Article : Google Scholar : PubMed/NCBI
22	Wang W, Peng B, Wang D, Ma X, Jiang D, Zhao J and Yu L: Human tumor microRNA signatures derived from large-scale oligo-nucleotide microarray datasets. Int J Cancer. 129:1624–1634. 2011. View Article : Google Scholar
23	Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stühler K, Meyer HE and Reifenberger G: Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain pathol. 20:539–550. 2010. View Article : Google Scholar
24	Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, Liu S, Schwind S, Santhanam R, Hickey CJ, et al: miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 140:652–665. 2010. View Article : Google Scholar : PubMed/NCBI
25	Pan YZ, Morris ME and Yu AM: MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol Pharmacol. 75:1374–1379. 2009. View Article : Google Scholar : PubMed/NCBI
26	Li WQ, Li YM, Tao BB, Lu YC, Hu GH, Liu HM, He J, Xu Y and Yu HY: Downregulation of ABCG2 expression in glioblastoma cancer stem cells with miRNA-328 may decrease their chemoresistance. Med Sci Monit. 16:HY27–HY30. 2010.PubMed/NCBI
27	Dacic S, Kelly L, Shuai Y and Nikiforova MN: miRNA expression profiling of lung adenocarcinomas: Correlation with mutational status. Mod Pathol. 23:1577–1582. 2010. View Article : Google Scholar : PubMed/NCBI
28	Arora S, Ranade AR, Tran NL, Nasser S, Sridhar S, Korn RL, Ross JT, Dhruv H, Foss KM, Sibenaller Z, et al: MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration. Int J Cancer. 129:2621–2631. 2011. View Article : Google Scholar : PubMed/NCBI
29	Delic S, Lottmann N, Stelzl A, Liesenberg F, Wolter M, Götze S, Zapatka M, Shiio Y, Sabel MC, Felsberg J, et al: MiR-328 promotes glioma cell invasion via SFRP1-dependent Wnt-signaling activation. Neuro-oncol. 16:179–190. 2014. View Article : Google Scholar :