The MicroRNA Expression Signature of Bladder Cancer by Deep Sequencing: the Functional Significance of the MiR-195/497 Cluster

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Feb 13

PMID 24520312

Citations 95

Authors

Toshihiko Itesako

Naohiko Seki

Hirofumi Yoshino

Takeshi Chiyomaru

Takeshi Yamasaki

Hideo Hidaka

Tomokazu Yonezawa

Nijiro Nohata

Takashi Kinoshita

Masayuki Nakagawa

Hideki Enokida

Affiliations

Soon will be listed here.

Abstract

Current genome-wide microRNA (miRNA) expression signature analysis using deep sequencing technologies can drive the discovery of novel cancer pathways regulated by oncogenic and/or tumor suppressive miRNAs. We determined the genome-wide miRNA expression signature in bladder cancer (BC) by deep sequencing technology. A total of ten small RNA libraries were sequenced (five BCs and five samples of histologically normal bladder epithelia (NBE)), and 13,190,619 to 18,559,060 clean small RNA reads were obtained. A total of 933 known miRNAs and 17 new miRNA candidates were detected in this analysis. Among the known miRNAs, a total of 60 miRNAs were significantly downregulated in BC compared with NBE. We also found that several miRNAs, such as miR-1/133a, miR-206/133b, let-7c/miR-99a, miR-143/145 and miR-195/497, were located close together at five distinct loci and constituted clustered miRNAs. Among these clustered miRNAs, we focused on the miR-195/497 cluster because this clustered miRNA had not been analyzed in BC. Transfection of mature miR-195 or miR-497 in two BC cell lines (BOY and T24) significantly inhibited cancer cell proliferation, migration and invasion, suggesting that the miR-195/497 cluster functioned as tumor suppressors in BC. Regarding the genes targeted by the miR-195/497 cluster, the TargetScan algorithm showed that 6,730 genes were putative miR-195/497 targets, and 113 significantly enriched signaling pathways were identified in this analysis. The "Pathways in cancer" category was the most enriched, involving 104 candidate target genes. Gene expression data revealed that 27 of 104 candidate target genes were actually upregulated in BC clinical specimens. Luciferase reporter assays and Western blotting demonstrated that BIRC5 and WNT7A were directly targeted by miR-195/497. In conclusion, aberrant expression of clustered miRNAs was identified by deep sequencing, and downregulation of miR-195/497 contributed to BC progression and metastasis. Tumor suppressive miRNA-mediated cancer pathways provide new insights into the potential mechanisms of BC oncogenesis.

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References

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2012. CA Cancer J Clin. 2012; 62(1):10-29. DOI: 10.3322/caac.20138. View

Yamasaki T, Yoshino H, Enokida H, Hidaka H, Chiyomaru T, Nohata N . Novel molecular targets regulated by tumor suppressors microRNA-1 and microRNA-133a in bladder cancer. Int J Oncol. 2012; 40(6):1821-30. DOI: 10.3892/ijo.2012.1391. View

Chen Y, Wang S, Wu X, Shen M, Chen Z, Chen X . Characterization of microRNAs expression profiling in one group of Chinese urothelial cell carcinoma identified by Solexa sequencing. Urol Oncol. 2011; 31(2):219-27. DOI: 10.1016/j.urolonc.2010.11.007. View

Xu T, Zhu Y, Xiong Y, Ge Y, Yun J, Zhuang S . MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology. 2009; 50(1):113-21. DOI: 10.1002/hep.22919. View

Li R, Li Y, Kristiansen K, Wang J . SOAP: short oligonucleotide alignment program. Bioinformatics. 2008; 24(5):713-4. DOI: 10.1093/bioinformatics/btn025. View

Noguchi S, Mori T, Hoshino Y, Maruo K, Yamada N, Kitade Y . MicroRNA-143 functions as a tumor suppressor in human bladder cancer T24 cells. Cancer Lett. 2011; 307(2):211-20. DOI: 10.1016/j.canlet.2011.04.005. View

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

Luke C, Tracey E, Stapleton A, Roder D . Exploring contrary trends in bladder cancer incidence, mortality and survival: implications for research and cancer control. Intern Med J. 2009; 40(5):357-62. DOI: 10.1111/j.1445-5994.2009.01980.x. View

Olive V, Jiang I, He L . mir-17-92, a cluster of miRNAs in the midst of the cancer network. Int J Biochem Cell Biol. 2010; 42(8):1348-54. PMC: 3681296. DOI: 10.1016/j.biocel.2010.03.004. View

10.

Kanwar J, Kamalapuram S, Kanwar R . Survivin signaling in clinical oncology: a multifaceted dragon. Med Res Rev. 2012; 33(4):765-89. DOI: 10.1002/med.21264. View

11.

Fei X, Qi M, Wu B, Song Y, Wang Y, Li T . MicroRNA-195-5p suppresses glucose uptake and proliferation of human bladder cancer T24 cells by regulating GLUT3 expression. FEBS Lett. 2012; 586(4):392-7. DOI: 10.1016/j.febslet.2012.01.006. View

12.

Ostenfeld M, Bramsen J, Lamy P, Villadsen S, Fristrup N, Sorensen K . miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors. Oncogene. 2009; 29(7):1073-84. DOI: 10.1038/onc.2009.395. View

13.

Creighton C, Reid J, Gunaratne P . Expression profiling of microRNAs by deep sequencing. Brief Bioinform. 2009; 10(5):490-7. PMC: 2733187. DOI: 10.1093/bib/bbp019. View

14.

Nelson K, Weiss G . MicroRNAs and cancer: past, present, and potential future. Mol Cancer Ther. 2008; 7(12):3655-60. DOI: 10.1158/1535-7163.MCT-08-0586. View

15.

Bian K, Fan J, Zhang X, Yang X, Zhu H, Wang L . MicroRNA-203 leads to G1 phase cell cycle arrest in laryngeal carcinoma cells by directly targeting survivin. FEBS Lett. 2012; 586(6):804-9. DOI: 10.1016/j.febslet.2012.01.050. View

16.

Ichimi T, Enokida H, Okuno Y, Kunimoto R, Chiyomaru T, Kawamoto K . Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int J Cancer. 2009; 125(2):345-52. DOI: 10.1002/ijc.24390. View

17.

Singh R, Saini N . Downregulation of BCL2 by miRNAs augments drug-induced apoptosis--a combined computational and experimental approach. J Cell Sci. 2012; 125(Pt 6):1568-78. DOI: 10.1242/jcs.095976. View

18.

Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N . Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2011; 106(2):405-13. PMC: 3261671. DOI: 10.1038/bjc.2011.462. View

19.

Haga C, Phinney D . MicroRNAs in the imprinted DLK1-DIO3 region repress the epithelial-to-mesenchymal transition by targeting the TWIST1 protein signaling network. J Biol Chem. 2012; 287(51):42695-707. PMC: 3522270. DOI: 10.1074/jbc.M112.387761. View

20.

Chhabra R, Dubey R, Saini N . Cooperative and individualistic functions of the microRNAs in the miR-23a~27a~24-2 cluster and its implication in human diseases. Mol Cancer. 2010; 9:232. PMC: 2940846. DOI: 10.1186/1476-4598-9-232. View