Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting notch1

Chao Zhang , Zhiyong Yao , Mingyang Zhu , Xin Ma , Taoping Shi , Hongzhao Li , Baojun Wang , Jinzhi Ouyang , Xu Zhang

Current Medical Science ›› 2012, Vol. 32 ›› Issue (3) : 375 -382.

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Current Medical Science ›› 2012, Vol. 32 ›› Issue (3) : 375 -382. DOI: 10.1007/s11596-012-0065-z
Article

Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting notch1

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Abstract

MicroRNAs (miRNAs or miRs) are a class of short, non-coding RNAs that participate in various oncological processes. This study aims to explore the roles of microRNA-34a (miR-34a) in invasive urothelial bladder carcinoma. miR-34a was transfected into bladder cancer cell lines 253J and J82. The miR-34a expression levels in tissues and cells were detected by using qRT-PCR. The Notch1 expression was detected by qRT-PCR and Western blotting. Cell migratory and invasive abilities were measured by Transwell chamber assay. Bioinformatics and luciferase assay were performed to predict and analyze the binding sites between miRNA-34a and Notch1. It was found that there was aberrant expression of miR-34a in bladder cancer tissues. Moreover, we revealed that ectopic expression of miR-34a suppressed cell migration and invasion, while forced expression of Notch1 increased cell migratory and invasive abilities. Finally, we observed that miR-34a transfection significantly down-regulated luciferase activity and reduced the mRNA and protein levels of Notch1. Our study concluded that microRNA-34a antagonizes Notch1 and inhibits cell migration and invasion of bladder cancer cells, which indicates the tumor-suppressive function of microRNA-34a in bladder cancer.

Keywords

microRNA-34a / urothelial carcinoma / migration / invasion / Notch1

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Chao Zhang, Zhiyong Yao, Mingyang Zhu, Xin Ma, Taoping Shi, Hongzhao Li, Baojun Wang, Jinzhi Ouyang, Xu Zhang. Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting notch1. Current Medical Science, 2012, 32(3): 375-382 DOI:10.1007/s11596-012-0065-z

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References

[1]

JemalA., BrayF., CenterM.M., et al.. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 69-90

[2]

FilipowiczW., BhattacharyyaS.N., SonenbergN.. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat Rev Genet, 2008, 9(2): 102-114

[3]

YektaS., ShihI.H., BartelD.P.. MicroRNA-directed cleavage of HOXB8 mRNA. Science, 2004, 304(5670): 594-596

[4]

ZhangY., ChaoT., LiR., et al.. MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. J Mol Med (Berl), 2009, 87(1): 43-51

[5]

DengS., CalinG.A., CroceC.M., et al.. Mechanisms of microRNA deregulation in human cancer. Cell Cycle, 2008, 7(17): 2643-2646

[6]

KongF., SunC., WangZ., et al.. miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1. J Huazhong Univ Sci Technol [Med Sci], 2011, 31(4): 543-549

[7]

MauvielA.. Cytokine regulation of metalloproteinase gene expression. J Cell Biochem, 1993, 53(4): 288-295

[8]

SpornM.B.. The war on cancer. Lancet, 1996, 347(9012): 1377-1381

[9]

LinF., WangX., JieZ., et al.. Inhibitory effects of miR-146b-5p on cell migration and invasion of pancreatic cancer by targeting MMP16. J Huazhong Univ Sci Technol [Med Sci], 2011, 31(4): 509-514

[10]

CrawfordM., BrawnerE., BatteK., et al.. MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. Biochem Biophys Res Commun, 2008, 373(4): 607-612

[11]

LiY., GuessousF., ZhangY., et al.. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res, 2009, 69(19): 7569-7576

[12]

LiuC., KelnarK., LiuB., et al.. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med, 2011, 17(2): 211-215

[13]

LiN., FuH., TieY., et al.. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett, 2009, 275(1): 44-53

[14]

Raver-ShapiraN., MarcianoE., MeiriE., et al.. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell, 2007, 26(5): 731-743

[15]

WelchC., ChenY., StallingsR.L.. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene, 2007, 26(34): 5017-5022

[16]

MieleL., MiaoH., NickoloffB.J.. NOTCH signaling as a novel cancer therapeutic target. Curr Cancer Drug Targets, 2006, 6(4): 313-323

[17]

BolosV., Grego-BessaJ., de la PompaJ.L.. Notch signaling in development and cancer. Endocr Rev, 2007, 28(3): 339-363

[18]

AiX., ZhangX.P., WuZ., et al.. Effect of silencing Notch1 on proliferation of bladder cancer cell line T24. J Shandong Univ-Health Sci (Chinese), 2009, 47(9): 53-57

[19]

Bin HafeezB., AdhamiV.M., AsimM., et al.. Targeted knockdown of Notch1 inhibits invasion of human prostate cancer cells concomitant with inhibition of matrix metalloproteinase-9 and urokinase plasminogen activator. Clin Cancer Res, 2009, 15(2): 452-459

[20]

WangZ., BanerjeeS., LiY., et al.. Down-regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Res, 2006, 66(5): 2778-2784

[21]

ChigurupatiS., VenkataramanR., BarreraD., et al.. Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness. Cancer Res, 2010, 70(1): 418-427

[22]

WangJ., FuL., GuF., et al.. Notch1 is involved in migration and invasion of human breast cancer cells. Oncol Rep, 2011, 26(5): 1295-1303

[23]

PangR.T., LeungC.O., YeT.M., et al.. MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis, 2010, 31(6): 1037-1044

[24]

ShiT.P., XuH., WeiJ.F., et al.. Association of low expression of notch-1 and jagged-1 in human papillary bladder cancer and shorter survival. J Urol, 2008, 180(1): 361-366

[25]

HuZ., AiQ., XuH., et al.. Fibulin-5 is down-regulated in urothelial carcinoma of bladder and inhibits growth and invasion of human bladder cancer cell line 5637. Urol Oncol, 2011, 29(4): 430-435

[26]

BabashahS., SoleimaniM.. The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer, 2011, 47(87): 1127-1137

[27]

HeijmansB.T., BoerJ.M., SuchimanH.E., et al.. A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res, 2003, 63(6): 1249-1253

[28]

MatsumotoH., MatsuyamaH., FukunagaK., et al.. Allelic imbalance at 1p36 may predict prognosis of chemoradiation therapy for bladder preservation in patients with invasive bladder cancer. Br J Cancer, 2004, 91(6): 1025-1031

[29]

VinallR.L., ZripollA., WangS., et al.. MiR-34a chemo-sensitizes bladder cancer cells to cisplatin treatment regardless of P53-Rb pathway status. Int J Cancer, 2011, 130(11): 2526-2538

[30]

GaurA., JewellD.A., LiangY., et al.. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res, 2007, 67(6): 2456-2468

[31]

YanD., ZhouX., ChenX., et al.. MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci, 2009, 50(4): 1559-1565

[32]

PotapovaI.A., GaudetteG.R., BrinkP.R., et al.. Mesenchymal stem cells support migration, extracellular matrix invasion, proliferation, and survival of endothelial cells in vitro. Stem Cells, 2007, 25(7): 1761-1768

[33]

BalintK., XiaoM., PinnixC.C., et al.. Activation of Notch1 signaling is required for beta-catenin-mediated human primary melanoma progression. J Clin Invest, 2005, 115(11): 3166-3176

[34]

WillertK., NusseR.. Beta-catenin: a key mediator of Wnt signaling. Curr Opin Genet Dev, 1998, 8(1): 95-102

[35]

LiuH., ChenA., GuoF., et al.. Influence of osteopontin short hairpin RNA on the proliferation and invasion of human renal cancer cells. J Huazhong Univ Sci Technol [Med Sci], 2010, 30(1): 61-68

[36]

DelboscS., GlorianM., Le PortA.S., et al.. The benefit of docosahexanoic acid on the migration of vascular smooth muscle cells is partially dependent on Notch regulation of MMP-2/-9. Am J Pathol, 2008, 172(5): 1430-1440

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