Infiltration related miRNAs in bladder urothelial carcinoma

Abstract

This study aimed to investigate infiltration related microRNAs (miRNAs) in bladder urothelial carcinoma (BUC). Twenty patients with BUC were enrolled and divided into 2 groups according to infiltration or not: infiltrating BUC group (n=12) and non-infiltrating BUC group (n=8). Gene chip was used to detect infiltration related miRNAs in the BUC samples. In other recruited 17 patients with BUC who were divided into infiltrating BUC samples (n=14) and non-infiltrating BUC samples (n=3), and in 4 BUC cell lines (EJ, 5637, T24 and BIU-87), the expression of miRNAs was assayed by using reverse transcription-polymerase chain reaction (RT-PCR). In infiltrating BUC group, as compared with non-infiltrating BUC group, there were 7 differentially expressed miRNAs: hsa-miR-29c, hsa-miR-200a, hsa-miR-378, hsa-miR-429, hsa-miR-200c and hsa-miR-141 were up-regulated, while hsa-miR-451 was down-regulated. In the BUC samples, the results of RT-PCR were consistent with those by the miRNA array. In the cancer cell lines, RT-PCR in T24 only revealed the similar expression pattern of miRNAs to that by the miRNA array. It is suggested that infiltration of BUC is related with different expression of miRNAs, which may provide a novel platform for further study on function and action mechanism of miRNAs.

Keywords

microRNA / bladder urothelial carcinoma / infiltration related miRNAs / reverse transcription-polymerase chain reaction

References

[1] FleshnerN.E., HerrH.W., StewartA.K., et al.. The national cancer data base report on bladder carcinoma. The American college of surgeons commission on cancer and the American cancer society. Cancer, 1996, 78(7): 1505-1513

[2] JingK.Z., GaoJ.P., ChengW.. Gene therapy for bladder cancer: past and future. J Med Postgrad, 2007, 20(8): 861-864

[3] XuF., GaoJ.P., ChengW.. MicroRNA and cancer. Dongnan Guofang Yiyao (Chinese), 2008, 10(6): 436-438

[4] LeeR.C., FeinbaumR.L., AmbrosV., et al.. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 1993, 75(5): 843-854

[5] ZhangB.H., PanX.P., CobbG.P., et al.. Plant microRNA: a small regulatory molecule with big impact. Dev Biol, 2006, 289(1): 3-16

[6] ChengA.M., ByromM.W., SheltonJ., et al.. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res, 2005, 33(4): 1290-1297

[7] EbleJ.E., SauterG., EpsteinJ.I., et al.. . Pathology and genetics tumours of the urinary system and male genital organs, 2004, Lyon, IARC Press, 96-117

[8] JohnsonS.M., GrosshansH., ShingaraJ., et al.. RAS is regulated by the let-7 microRNA family. Cell, 2005, 120(5): 635-647

[9] CimminoA., CalinG.A., FabbriM., et al.. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA, 2005, 102: 13944-13949

[10] IorioM.V., FerracinM., LiuC. e. a1.. MicroRNA gene expression deregulation in human breast cancer. Cancer Res, 2005, 65(16): 7065-7070

[11] MichaelM.Z., O’ConnorS.M., van Holst PellekaanN. e. a1.. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res, 2003, 1(12): 882-891

[12] HeL., HeX., LoweS.W., et al.. MicroRNAs join the p53 network-another piece in the tumor-suppression puzzle. Nat Rev Cancer, 2007, 7(11): 819-822

[13] LuJ., GetzG., MiskaE.A., et al.. MicroRNA expression profiles classify human cancers. Nature, 2005, 435(7043): 834-838

[14] VoliniaS., CalinG.A., LiuC.G., et al.. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA, 2006, 103(7): 2257-2261

[15] CardiffR.D.. Epithelial to mesenchymal transition tumors: fallacious or snail’s pace?. Clin Cancer Res, 2005, 11(24Pt1): 8534-8553

[16] ThompsonE.W., NewgreenD.F., TarinD.. Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition?. Cancer Res, 2005, 65(14): 5991-5995

[17] GregoryP.A., BrackenC.P., BertA.G., et al.. MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle, 2008, 7(20): 3112-3118

[18] GregoryP.A., BertA.G., PatersonE.L., et al.. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biol, 2008, 10(5): 593-601

[19] ParkS.M., GaurA.B., LengyelE., et al.. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev, 2008, 22(7): 894-907

[20] KorpalM., LeeE.S., HuG., et al.. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem, 2008, 283(22): 14910-14914

[21] BurkU., SchubertJ., WellnerU., et al.. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep, 2008, 9(6): 521-522

[22] KongW., YangH., HeL., et al.. MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol, 2008, 28(22): 6773-6784

[23] NegriniM., CalinG.A.. Breast cancer metastasis: a microRNA story. Breast Cancer Res, 2008, 10(2): 203

[24] HuangQ., GumireddyK., SchrierM., et al.. The microRNAs miR-373 and miR-520c promote tumor invasion and metastasis. Nat Cell Biol, 2008, 10(2): 202-210

[25] ZhuS., WuH., WuF., et al.. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res, 2008, 18(3): 350-359

[26] AsanganiI.A., RasheedS.A., NikolovaD.A., et al.. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene, 2008, 27(15): 2128-2136

[27] LiT., LiD., ShaJ., et al.. MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun, 2009, 383(3): 280-285

[28] YangK., HandoreanA.M., IczkowskiK.A.. MicroRNAs 373 and 520c are downregulated in prostate cancer, suppress CD44 translation and enhance invasion of prostate cancer cells in vitro. Int J Clin Exp Pathol, 2009, 2(4): 361-369

[29] GandelliniP., FoliniM., LongoniN., et al.. miR-205 exerts tumor-suppressive functions in human prostate through downregulation of protein kinase Cepsilon. Cancer Res, 2009, 69(6): 2287-2295