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http://dx.doi.org/10.14456/apjcp.2016.114/PJCP.2016.17.7.3437

Roles of MicroRNA-21 and MicroRNA-29a in Regulating Cell Adhesion Related Genes in Bone Metastasis Secondary to Prostate Cancer  

Mohamad, Maisarah (Department of Physiology, Faculty of Medicine, Hospital UKM)
Wahab, Norhazlina Abdul (Department of Physiology, Faculty of Medicine, Hospital UKM)
Yunus, Rosna (Histopathology Unit, Department of Pathology, Hospital Kuala Lumpur)
Murad, Nor AzianAbdul (UKM Molecular Biology Institute (UMBI), Hospital UKM)
Zainuddin, Zulkifli Md (Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, Universiti Kebangsaan Malaysia (UKM))
Sundaram, Murali (Urology Department, Hospital Kuala Lumpur)
Mokhtar, Norfilza Mohd (Department of Physiology, Faculty of Medicine, Hospital UKM)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.7, 2016 , pp. 3437-3445 More about this Journal
Abstract
Background: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be down-regulated in clinical samples, most likely due to the post-transcriptional modification by microRNAs. Targeted genes would be up-regulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors. Materials and Methods: MicroRNA software predicted that miR-21 targets VCL while miR-29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalin-fixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE-1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels. Results: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down-regulated while CX3CL1 was up-regulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly upregulated while CX3CL1 mRNA was significantly down-regulated compared to the RWPE-1 case. Conclusions: The down-regulation of VCL in FFPE specimens is most likely regulated by miR-21 based on the in vitro evidence but the exact mechanism of how miR-21 can regulate VCL is unclear. Up-regulated in CaP, CX3CL1 was found not regulated by miR-29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNA-mRNA interactions may provide additional knowledge for individualized study of cancers.
Keywords
Prostate cancer; bone metastasis; miR-21; miR-29a; VCL; CX3CL1;
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1 Murphy DA, Courtneidge SA (2012). The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function. Nat Rev Mol Cell Biol, 12, 413-26
2 Volinia S, Galasso M, Costinean S, et al (2010). Reprogramming of miRNA networks in cancer and leukemia. Genome Res, 20, 589-99   DOI
3 Watahiki A, Wang Y, Morris J, et al (2011). MicroRNAs associated with metastatic prostate cancer. PLoS ONE, 6, 24950.   DOI
4 Wong YC, Tam NNC (2002). Dedifferentiation of stromal smooth muscle as a factor in prostate carcinogenesis. Differentiation, 70, 633-45   DOI
5 Yoshimoto T, Takinoa T, Lia Z, et al (2014). Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway. Biochem Biophys Res Commun, 455, 251-5   DOI
6 Zhu LY, Zhong KB, Lu SX, et al (2010). Vinculin and the androgen receptor in prostate cancer: expressions and correlations. Zhonghua Nan KeXue, 16, 794-8
7 Zhu S, Wu H, Wu F, et al (2008). MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res, 18, 350-9   DOI
8 Alenghat FJ, Fabry B, Tsai KY, et al (2000). Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer. Biochem Biophys Res Commun, 277, 93-9   DOI
9 Ooi WL, Brown A, Ramakrishnan S, et al (2012). Comparison of prostate cancer diagnosis and tumour characteristics between urban and rural patients in Western Australia. BJU International, 109, 8-61
10 Pekarsky Y, Santanam U, Cimmino A, et al (2006). Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res, 66, 11590-3   DOI
11 Pekarsky Y, Croce CM (2009). Is miR-29 an oncogene or tumor suppressor in CLL? Oncotarget, 1, 224-7.
12 Pratt AJ, MacRae IJ (2009). The RNA-induced silencing complex: a versatile gene-silencing machine. J Biol. Chem, 284, 17897-901   DOI
13 Rodriguez Fernandez JL, Geiger B, Salomon D, et al (1992). Overexpression of vinculin suppresses cell motility in BALB/c 3t3 cells. Cell Motility Cytoskeleton, 22, 127-34   DOI
14 Rubashkin MG, Cassereau L, Bainer R, et al (2015). Force engages vinculin and promotes tumor progression by enhancing PI3K activation of phosphatidylinositol (3,4,5)-triphosphate. Cancer Res, 74, 4597-611
15 Ruiz C, Holz DR, Oeggerli M, et al (2011). Amplification and overexpression of vinculin are associated with increased tumour cell proliferation and progression in advanced prostate cancer. J Pathol, 223, 543-52   DOI
16 Sabatel C, Malvaux L, Bovy N, et al (2011). MicroRNA-21 Exhibits Antiangiogenic Function by Targeting RhoB Expression in Endothelial Cells. PLoS ONE, 6, 16979   DOI
17 Salwa SIA, Ayman SA (2015). A study evaluating prevalence of hypertension and risk factors affecting on blood pressure control among type 2 diabetes patients attending teaching hospital in Malaysia. Diabetes Metabolic Syndrome, 7, 83-6.   DOI
18 Berrier AL, Yamada KM (2007). Cell-matrix adhesion. J Cell Physiol, 213, 565-73   DOI
19 Alwan A, MacLean DR, Riley LM, et al (2010). Monitoring and surveillance of chronic non-communicable diseases: progress and capacity in high-burden countries. Lancet, 376, 1861-8   DOI
20 Aniqua R, Carey SP, Goldblatt ZE, et al (2016). Vinculin regulates directionality and cell polarity in two- and threedimensional matrix and three-dimensional microtrack migration. Mol Biol Cell, 27, 1431-41   DOI
21 Blum DL, Koyama T, M'Koma AE, et al (2008). Chemokine markers predict biochemical recurrence of prostate cancer following prostatectomy. Clin Cancer Res, 14, 7790-97   DOI
22 Liu DF, Wu JT, Wang JM, et al (2012). MicroRNA expression profile analysis reveals diagnostic biomarker for human prostate cancer. Asian Pac J Cancer Prev, 13, 3313-17.   DOI
23 Lewis BP, Burge CB, Bartel DP (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120, 15-20   DOI
24 Li T, Li D, Sha J, et al (2009). MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun, 383, 280-85   DOI
25 Li T, Guo H, Song Y, et al (2014). Loss of vinculin and membrane-bound ${\beta}$-catenin promotes metastasis and predicts poor prognosis in colorectal cancer. Molecular Cancer, 13, 1-15   DOI
26 Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-Delta Delta CT Method. Methods, 25, 402-8   DOI
27 Lucas AD, Chadwick N, Warren BF, et al (2001). The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo. Am J Pathol, 158, 855 -66   DOI
28 Lukk M, Kapushesky M, Nikkila J, et al (2010). A global map of human gene expression. Nat Biotechnol, 28, 322-4   DOI
29 Mierke CT (2009) The role of vinculin in the regulation of the mechanical properties of cells. Cell Biochem Biophys. 53, 115-26   DOI
30 Mattie MD, Benz CC, Bowers J, et al (2006). Optimized highthroughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Molecular Cancer, 5, 1-14
31 Mishra S, Deng JJ, Gowda PS, et al (2014). Androgen receptor and microRNA-21 axis downregulates transforming growth factor beta receptor II (TGFBR2) expression in prostate cancer. Oncogene, 33, 4097-106   DOI
32 Shih W, Yamada S (2012). N-cadherin-mediated cell-cell adhesion promotes cell migration in a three-dimensional matrix. J Cell Sci, 125, 3661-70   DOI
33 Chum PY, Haas A, Kelley M (2012). Solution for RT-qPCR: relative gene expression analysis using thermo scientific pikoreal real-time pcr system and solaris gene expression reagents. thermo scientific technical note, http://www.thermo.com.cn/Resources/201306/2114332215.pdf
34 Coarfa C, Fiskus W, Eedunuri VK, et al (2015). Comprehensive proteomic profiling identifies the androgen receptor axis and other signaling pathways as targets of microRNAs suppressed in metastatic prostate cancer. Oncogene, 35, 2345-56
35 Coppola V, Maria RD, eBonci D (2010). MicroRNAs and prostate cancer. Endocrine-Related Cancer, 17, 1-17   DOI
36 Sarker D, Reid AHM, Yap TA, et al (2009). Targeting the PI3K/AKT pathway for the treatment of prostate cancer. Clin Cancer Res, 15, 4799-805   DOI
37 Schramedei K, Morbt N, Pfeifer G, et al (2011). MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4. Oncogene, 30, 2975-85.   DOI
38 Shukla S, MacLennan GT, Hartman DJ, et al (2007). Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int J Cancer, 121, 1424-32   DOI
39 Shulby SA, Dolloff NG, Stearns ME, et al (2004). CX3CR1-fractalkine expression regulates cellular mechanisms involved in adhesion, migration, and survival of human prostate cancer cells. Cancer Res, 64, 4693-98   DOI
40 Strobel S, Grunblatt E, Riederer P, et al (2015). Changes in the expression of genes related to neuroinflammation over the course of sporadic Alzheimer's disease progression: CX3CL1, TREM2, and PPARc. J Neural Transm, 122, 1069-1076   DOI
41 Sun Z, Liu F (2013). Association of Nox1 and vinculin with colon cancer progression. Cancer Invest, 31, 273-8.   DOI
42 Thievessen I, Fakhri N, Steinwachs J, et al (2015). Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen. FASEB J, 29, 4555-67   DOI
43 Thomson DW, Bracken CP, Goodall GJ (2011). Survey and summary: experimental strategies for microRNA target identification. Nucleic Acids Res, 39, 6845-53   DOI
44 Ezzell RM, Goldman WH, Wan N, et al (1997). Vinculin promotes cell spreading by mechanically coupling integrins to the cytoskeleton. Experimental Cell Res, 231, 14-26   DOI
45 Cui Y, Yamada S (2013). N-cadherin dependent collective cell invasion of prostate cancer cells is regulated by the N-Terminus of ${\alpha}$-Catenin. PLoS ONE, 8, 55069   DOI
46 DeMali KA, Burridge K (2003). Coupling membrane protrusion and cell adhesion. J Cell Science, 116, 2389-97   DOI
47 Desai M, Ma T,Chellaiah MA (2008). Invadopodia and matrix degradation, a new property of prostate cancer cells during migration and invasion. J Biological Chem, 283, 13856-66   DOI
48 Fang Z, Rajewsky N (2011). The impact of miRNA target sites in coding sequences and in 39UTRs. PLoS ONE, 6, 18067   DOI
49 Buscaglia LEB, Li Y (2011). Apoptosis and the target genes of miR-21. Chin J Cancer, 30, 371-80   DOI
50 Folini M, Gandellini P, Longoni N, et al (2010). miR-21 : an oncomir on strike in prostate cancer. Molecular Cancer, 9,12   DOI
51 Guang-yuan Y, Hai-feng Z, Feng X, et al (2012). Downregulation of vinculin in human colorectal carcinoma identified by proteomics analysis. Chem Res Chinese Universities, 28, 1031-34
52 Toma-Jonik A, Widlak W, Korfanty J, et al (2015). Active heat shock transcription factor 1 supports migration of the melanoma cells via vinculin down-regulation. Cellular Signalling, 27, 304-401
53 Gandellini P, Folini M, Zaffaroni N (2010). Emerging role of microRNAs in prostate cancer: implications for personalized medicine. Discovery Med, 9, 212-8
54 Gaudin F, Nasreddine S, Donnadieu AC, et al (2011). Identification of the chemokine CX3CL1 as a new regulator of malignant cell proliferation in epithelial ovarian cancer. PLoS ONE, 6, 21546   DOI
55 Geiger B, Yamada KM (2011). Molecular Architecture and Function of Matrix Adhesions. Cold Spring Harbor Perspect Biol, 3, 5033   DOI
56 Giovannucci E, Harlan DM, Archer MC, et al (2010). Diabetes and cancer: a consensus report. Ca Cancer J Clin, 60, 207-21   DOI
57 Gorlov IP, Sircar K, Zhao H, et al (2010). Prioritizing genes associated with prostate cancer development. BMC Cancer, 10, 1-8   DOI
58 Gregg JL, Brown KE, Mintz EM, Piontkivska H, Fraizer GC (2010). Analysis of gene expression in prostate cancer epithelial and interstitial stromal cells using laser capture microdissection. BMC Cancer, 10, 1-14   DOI
59 Han M, Liu M, Wang Y, et al (2012). Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PLoS ONE, 7, 39520   DOI
60 Hong GE, Christopher HCK, Singam P, et al (2010). Seven-year review of prostate carcinomas diagnosed by TRUS biopsy in a single Malaysian institution. Asian Pac J Cancer Prev, 11, 1351-53
61 Ishiyama N, Tanaka N, Abe K (2013). An autoinhibited structure of ${\alpha}$-catenin and its implications for vinculin recruitment to adherens junctions. J Bio Chem, 288, 15913-25   DOI
62 Kaboteh R, Damber JE, Gjertsson P, et al (2013). Bone Scan Index: a prognostic imaging biomarker for high-risk prostate cancer patients receiving primary hormonal therapy. EJNMMI Res, 3, 3-6   DOI
63 Tomlins SA, Mehra R, Rhodes DR, et al (2007). Integrative molecular concept modeling of prostate cancer progression. Nature Genetics, 39, 41-51   DOI
64 Torre LA, Bray F, Siegel RL, et al (2015). Global cancer statistics, 2012. Ca Cancer J Clin, 65, 87-108   DOI
65 Trevino V, Tadesse MG, Vannucci M, et al (2011). Analysis of normal-tumour tissue interaction in tumours: prediction of prostate cancer features from the molecular profile of adjacent normal cells. PLoS ONE, 6, 16492.   DOI
66 Vindrieux D, Escobar P, Lazennec G (2009). Emerging roles of chemokines in prostate cancer. Endocrine-Related Cancer, 16, 663-73   DOI
67 Jamieson WL, Shimizu S, D'Ambrosio JA, et al (2008). CX3CR1 is expressed by prostate epithelial cells and androgens regulate the levels of CX3CL1/fractalkine in the bone marrow: potential role in prostate cancer bone tropism. Cancer Res, 68, 1715-22   DOI
68 Jemal A, Siegel R, Xu J, Ward, E (2010). Cancer Statistics. CA Cancer J Clin, 60, 277-300   DOI
69 Jiang K, Sun J, Cheng J, et al (2004). Akt mediates ras downregulation of rhob, a suppressor of transformation, invasion, and metastasis. Mol Cell Biol, 24, 5565-76.   DOI
70 Kao J, Jani AB, Vijayakumar S (2004). Is there an association between multiple myeloma and prostate cancer? Med Hypotheses, 63, 226-31   DOI
71 Kapinas K, Kessler CB, Delany AM (2009). miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signaling. J Cell Biochem, 108, 216-24   DOI
72 Kapinas K, Kessler C, Ricks T, et al (2010). miR-29 modulates wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem, 285, 25221-31   DOI
73 Kawakami K, Fujita Y, Kato T, et al (2015). Integrin ${\beta}$4 and vinculin contained in exosomes are potential markers for progression of prostate cancer associated with taxaneresistance. Int J Oncol, 47, 384-90   DOI
74 Koizumi K, Saitoh Y, Minami T, et al (2009). Role of CX3CL1/fractalkine in osteoclast differentiation and bone resorption. J Immunol, 183, 7825-31   DOI
75 Le Duc Q, Shi Q, Blonk I, et al (2010). Vinculin potentiates E-cadherin mechanosensing and is recruited to actinanchored sites within adherens junctions in a myosin II-dependent manner. J Cell Biol, 189, 1107-15   DOI