Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Prostate Cancer | Primary research

Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial–mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2

Authors: Zhenming Jiang, Yuxi Zhang, Xi Chen, Pingeng Wu, Dong Chen

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

Prostate cancer (PCa) is a common disease that often occurs among older men and a frequent cause of malignancy associated death in this group. microRNA (miR)-129-5p has been identified as an essential regulator with a significant role in the prognosis of PC. Therefore, this study aimed to investigate roles of miR-129-5p in PCa.

Methods

Microarray analysis was conducted to identify PCa-related genes. The expression of miR-129-5p and ZIC2 in PCa tissues was investigated. To understand the role of miR-129-5p and ZIC2 in PCa, DU145 cells were transfected with mimic or inhibitor of miR-129-5p, or si-ZIC2 and the expression of Wnt, β-catenin, E-cadherin, vimentin, N-cadherin, vascular endothelial growth factor (VEGF), and CD31, as well as the extent of β-catenin phosphorylation was determined. In addition, cell proliferation, migration, invasion, angiogenesis, apoptosis and tumorigenesis were detected.

Results

miR-129-5p was poorly expressed and ZIC2 was highly expressed in PCa tissues. Down-regulation of ZIC2 or overexpression of miR-129-5p reduced the expression of ZIC2, Wnt, β-catenin, N-cadherin, vimentin, and β-catenin phosphorylation but increased the expression of E-cadherin. Importantly, miR-129-5p overexpression significantly reduced cell migration, invasion, angiogenesis and tumorigenesis while increasing cell apoptosis.

Conclusions

The findings of the present study indicated that overexpression of miR-129-5p or silencing of ZIC2 could inhibit epithelial–mesenchymal transition (EMT) and angiogenesis in PCa through blockage of the Wnt/β-catenin signaling pathway.
Literature
1.
Perner S, Cronauer MV, Schrader AJ, Klocker H, Culig Z, Baniahmad A. Adaptive responses of androgen receptor signaling in castration-resistant prostate cancer. Oncotarget. 2015;6(34):35542–55.PubMedPubMedCentralCrossRef
2.
El-Haibi CP, Singh R, Gupta P, Sharma PK, Greenleaf KN, Singh S, Lillard JW Jr. Antibody microarray analysis of signaling networks regulated by Cxcl13 and Cxcr5 in prostate cancer. J Proteomics Bioinform. 2012;5(8):177–84.PubMedPubMedCentralCrossRef
3.
4.
Loberg RD, Logothetis CJ, Keller ET, Pienta KJ. Pathogenesis and treatment of prostate cancer bone metastases: targeting the lethal phenotype. J Clin Oncol. 2005;23(32):8232–41.PubMedCrossRef
5.
Grubb RL 3rd, Kibel AS. Prostate cancer: screening, diagnosis and management in 2007. Mo Med. 2007;104(5):408–13 (quiz 13–4).PubMed
6.
7.
8.
Lamouille S, Subramanyam D, Blelloch R, Derynck R. Regulation of epithelial–mesenchymal and mesenchymal–epithelial transitions by microRNAs. Curr Opin Cell Biol. 2013;25(2):200–7.PubMedPubMedCentralCrossRef
9.
Zhang J, Kuang Y, Wang Y, Xu Q, Ren Q. Notch-4 silencing inhibits prostate cancer growth and EMT via the NF-kappaB pathway. Apoptosis. 2017;22(6):877–84.PubMedCrossRef
10.
Mukherji D, Temraz S, Wehbe D, Shamseddine A. Angiogenesis and anti-angiogenic therapy in prostate cancer. Crit Rev Oncol Hematol. 2013;87(2):122–31.PubMedCrossRef
11.
12.
Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM. Delivering the promise of miRNA cancer therapeutics. Drug Discov Today. 2013;18(5–6):282–9.PubMedCrossRef
13.
Yu Y, Zhao Y, Sun XH, Ge J, Zhang B, Wang X, Cao XC. Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial–mesenchymal transition and is associated with poor prognosis in breast cancer. Oncotarget. 2015;6(33):34423–36.PubMedPubMedCentralCrossRef
14.
Xu S, Yi XM, Zhang ZY, Ge JP, Zhou WQ. miR-129 predicts prognosis and inhibits cell growth in human prostate carcinoma. Mol Med Rep. 2016;14(6):5025–32.PubMedPubMedCentralCrossRef
15.
Luo Z, Gao X, Lin C, Smith ER, Marshall SA, Swanson SK, Florens L, Washburn MP, Shilatifard A. Zic2 is an enhancer-binding factor required for embryonic stem cell specification. Mol Cell. 2015;57(4):685–94.PubMedPubMedCentralCrossRef
16.
Ma G, Dai W, Sang A, Yang X, Li Q. Roles of ZIC family genes in human gastric cancer. Int J Mol Med. 2016;38(1):259–66.PubMedCrossRef
17.
Hoogland AM, Bottcher R, Verhoef E, Jenster G, van Leenders GJ. Gene-expression analysis of gleason grade 3 tumor glands embedded in low- and high-risk prostate cancer. Oncotarget. 2016;7(25):37846–56.PubMedPubMedCentralCrossRef
18.
19.
Wang S, Chen Y, Yu X, Lu Y, Wang H, Wu F, Teng L. miR-129-5p attenuates cell proliferation and epithelial mesenchymal transition via HMGB1 in gastric cancer. Pathol Res Pract. 2019;215(4):676–82.PubMedCrossRef
20.
21.
Zhang P, Li J, Song Y, Wang X. MiR-129-5p inhibits proliferation and invasion of chondrosarcoma cells by regulating SOX4/Wnt/beta-catenin signaling pathway. Cell Physiol Biochem. 2017;42(1):242–53.PubMedCrossRef
22.
Pasoglou V, Larbi A, Collette L, Annet L, Jamar F, Machiels JP, Michoux N, Vande Berg BC, Tombal B, Lecouvet FE. One-step TNM staging of high-risk prostate cancer using magnetic resonance imaging (MRI): toward an upfront simplified “all-in-one” imaging approach? Prostate. 2014;74(5):469–77.PubMedCrossRef
23.
Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 1999;59(22):5830–5.PubMed
24.
Yu H, Li X, Sun S, Gao X, Zhou D. c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation. Biochem Biophys Res Commun. 2012;427(3):659–65.PubMedCrossRef
25.
Ayuk SM, Abrahamse H, Houreld NN. The role of photobiomodulation on gene expression of cell adhesion molecules in diabetic wounded fibroblasts in vitro. J Photochem Photobiol B. 2016;161:368–74.PubMedCrossRef
26.
Arunkumar R, Sharmila G, Elumalai P, Senthilkumar K, Banudevi S, Gunadharini DN, Benson CS, Daisy P, Arunakaran J. Effect of diallyl disulfide on insulin-like growth factor signaling molecules involved in cell survival and proliferation of human prostate cancer cells in vitro and in silico approach through docking analysis. Phytomedicine. 2012;19(10):912–23.PubMedCrossRef
27.
McCabe CD, Spyropoulos DD, Martin D, Moreno CS. Genome-wide analysis of the homeobox C6 transcriptional network in prostate cancer. Cancer Res. 2008;68(6):1988–96.PubMedPubMedCentralCrossRef
28.
Waltregny D, Alami Y, Clausse N, de Leval J, Castronovo V. Overexpression of the homeobox gene HOXC8 in human prostate cancer correlates with loss of tumor differentiation. Prostate. 2002;50(3):162–9.PubMedCrossRef
29.
30.
Weirick T, Militello G, Ponomareva Y, John D, Doring C, Dimmeler S, Uchida S. Logic programming to infer complex RNA expression patterns from RNA-seq data. Brief Bioinform. 2018;19(2):199–209.PubMed
31.
Wang D, Lu G, Shao Y, Xu D. MiR-182 promotes prostate cancer progression through activating Wnt/beta-catenin signal pathway. Biomed Pharmacother. 2018;99:334–9.PubMedCrossRef
32.
Quinn DI, Shore ND, Egawa S, Gerritsen WR, Fizazi K. Immunotherapy for castration-resistant prostate cancer: progress and new paradigms. Urol Oncol. 2015;33(5):245–60.PubMedCrossRef
33.
Deng K, Wang H, Guo X, Xia J. The cross talk between long, non-coding RNAs and microRNAs in gastric cancer. Acta Biochim Biophys Sin (Shanghai). 2016;48(2):111–6.CrossRef
34.
35.
Valentino A, Calarco A, Di Salle A, Finicelli M, Crispi S, Calogero RA, Riccardo F, Sciarra A, Gentilucci A, Galderisi U, Margarucci S, Peluso G. Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences. Oncogene. 2017;36(43):6030–40.PubMedCrossRef
36.
Li Y, An H, Pang J, Huang L, Li J, Liu L. MicroRNA profiling identifies miR-129-5p as a regulator of EMT in tubular epithelial cells. Int J Clin Exp Med. 2015;8(11):20610–6.PubMedPubMedCentral
37.
Luan QX, Zhang BG, Li XJ, Guo MY. MiR-129-5p is downregulated in breast cancer cells partly due to promoter H3K27m3 modification and regulates epithelial–mesenchymal transition and multi-drug resistance. Eur Rev Med Pharmacol Sci. 2016;20(20):4257–65.PubMed
38.
Wang R, Zhao N, Li S, Fang JH, Chen MX, Yang J, Jia WH, Yuan Y, Zhuang SM. MicroRNA-195 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting the expression of VEGF, VAV2, and CDC42. Hepatology. 2013;58(2):642–53.PubMedCrossRef
39.
Xu S, Ge J, Zhang Z, Zhou W. MiR-129 inhibits cell proliferation and metastasis by targeting ETS1 via PI3K/AKT/mTOR pathway in prostate cancer. Biomed Pharmacother. 2017;96:634–41.PubMedCrossRef
40.
Shen N, Huang X, Li J. Upregulation of miR-129-5p affects laryngeal cancer cell proliferation, invasiveness, and migration by affecting STAT3 expression. Tumour Biol. 2016;37(2):1789–96.PubMedCrossRef
41.
Xu H, Hu Y, Qiu W. Potential mechanisms of microRNA-129-5p in inhibiting cell processes including viability, proliferation, migration and invasiveness of glioblastoma cells U87 through targeting FNDC3B. Biomed Pharmacother. 2017;87:405–11.PubMedCrossRef
42.
Brest P, Lassalle S, Hofman V, Bordone O, Gavric Tanga V, Bonnetaud C, Moreilhon C, Rios G, Santini J, Barbry P, Svanborg C, Mograbi B, Mari B, Hofman P. MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells. Endocr Relat Cancer. 2011;18(6):711–9.PubMedCrossRef
43.
Liu KX, Edwards B, Lee S, Finelli MJ, Davies B, Davies KE, Oliver PL. Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis. Brain. 2015;138(Pt 5):1167–81.PubMedPubMedCentralCrossRef
44.
Qiao B, He BX, Cai JH, Tao Q, King-Yin Lam A. MicroRNA-27a-3p modulates the Wnt/beta-catenin signaling pathway to promote epithelial-mesenchymal transition in oral squamous carcinoma stem cells by targeting SFRP1. Sci Rep. 2017;7:44688.PubMedPubMedCentralCrossRef
45.
Wang YP, Guo PT, Zhu Z, Zhang H, Xu Y, Chen YZ, Liu F, Ma SP. Pleomorphic adenoma gene like-2 induces epithelial–mesenchymal transition via Wnt/beta-catenin signaling pathway in human colorectal adenocarcinoma. Oncol Rep. 2017;37(4):1961–70.PubMedPubMedCentralCrossRef
46.
Azarin SM, Lian X, Larson EA, Popelka HM, de Pablo JJ, Palecek SP. Modulation of Wnt/beta-catenin signaling in human embryonic stem cells using a 3-D microwell array. Biomaterials. 2012;33(7):2041–9.PubMedCrossRef
Metadata
Title
Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial–mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2
Authors
Zhenming Jiang
Yuxi Zhang
Xi Chen
Pingeng Wu
Dong Chen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0977-9

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue

Primary research

Comprehensive bioinformatics analysis reveals potential lncRNA biomarkers for overall survival in patients with hepatocellular carcinoma: an on-line individual risk calculator based on TCGA cohort

Retraction Note

Retraction Note: Overexpression of A613T and G462T variants of DNA polymerase β weakens chemotherapy sensitivity in esophageal cancer cell lines

Primary research

β-Asarone increases doxorubicin sensitivity by suppressing NF-κB signaling and abolishes doxorubicin-induced enrichment of stem-like population by destabilizing Bmi1

Primary research

TMED3 promotes cell proliferation and motility in breast cancer and is negatively modulated by miR-188-3p

Primary research

Markers of MEK inhibitor resistance in low-grade serous ovarian cancer: EGFR is a potential therapeutic target

Primary research

Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits