Gene expression profiling of microRNAs associated with UCA1 in bladder cancer cells

Xie,Xiaojuan; Pan,Jingjing; Wei,Liqiang; Wu,Shouzhen; Hou,Huilian; Li,Xu; Chen,Wei

doi:10.3892/ijo.2016.3357

Gene expression profiling of microRNAs associated with UCA1 in bladder cancer cells

Authors:
- Xiaojuan Xie
- Jingjing Pan
- Liqiang Wei
- Shouzhen Wu
- Huilian Hou
- Xu Li
- Wei Chen
View Affiliations

Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Shaanxi Center for Clinical Laboratory, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: January 25, 2016 https://doi.org/10.3892/ijo.2016.3357
Pages: 1617-1627

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Emerging evidence indicates that non-coding RNAs, such as lncRNAs and microRNAs, play important roles in diverse diseases, such as cancer, immune diseases and cardiovascular diseases. Interestingly, lncRNAs could directly or indirectly regulate the expression of miRNAs. However, the expression profiling of miRNAs associated with UCA1 in bladder cancer remains unknown. Here, we used Illumina deep sequencing to sequence miRNA libraries from both the UCA1 knockdown and normal high-expression 5637 cells. We identified 225 and 235 miRNAs expressed in 5637 cells of normal high-expression and knockdown of UCA1, respectively. Overall, expression of 75 miRNAs showed significant difference associated with UCA1, of which 38 were upregulated and 37 downregulated with UCA1 knockdown. GO analysis of the host target genes revealed that these aberrantly regulated miRNAs were involved in complex cellular pathways, including biological process, cellular component and molecular function. We selected 8 candidate miRNAs associated with UCA1 and predicted their targeted mRNAs, and found that p27kip1 was a crucial downstream molecule for these 8 miRNAs, especially for miR-196a. KEGG pathway analysis showed that PI3K-Akt signaling pwathway was involved in regulating these 8 candidant miRNAs. Among these 8 candidant miRNAs, we observed the correlation among UCA1, miR-196a and the host target mRNA, p27kip1, in bladder cancer cells and tissues. UCA1 was upregulated by miR-196a and positively correlated with miR-196a, whereas UCA1 and miR-196a were negatively correlated with p27kip1, which was downregulated in bladder cancer patients. Thus, our findings provided valuable information on miRNAs associated with UCA1 in bladder cancer, which could be helpful to further explore the related genes and molecular networks fundamental in bladder cancer progression.

View Figures

View References

1	Volders PJ, Helsens K, Wang X, Menten B, Martens L, Gevaert K, Vandesompele J and Mestdagh P: LNCipedia: A database for annotated human lncRNA transcript sequences and structures. Nucleic Acids Res. 41:D246–D251. 2013. View Article : Google Scholar :
2	ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 489:57–74. 2012. View Article : Google Scholar : PubMed/NCBI
3	Nagano T and Fraser P: No-nonsense functions for long noncoding RNAs. Cell. 145:178–181. 2011. View Article : Google Scholar : PubMed/NCBI
4	Wapinski O and Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol. 21:354–361. 2011. View Article : Google Scholar : PubMed/NCBI
5	Gibb EA, Brown CJ and Lam WL: The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 10:382011. View Article : Google Scholar : PubMed/NCBI
6	Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI
7	Wang X, Song X, Glass CK and Rosenfeld MG: The long arm of long noncoding RNAs: Roles as sensors regulating gene transcriptional programs. Cold Spring Harb Perspect Biol. 3:a0037562011. View Article : Google Scholar
8	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
9	Salmena L, Poliseno L, Tay Y, Kats L and Pandolfi PP: A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language? Cell. 146:353–358. 2011. View Article : Google Scholar : PubMed/NCBI
10	Thomas M, Lieberman J and Lal A: Desperately seeking microRNA targets. Nat Struct Mol Biol. 17:1169–1174. 2010. View Article : Google Scholar : PubMed/NCBI
11	Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, et al: Landscape of transcription in human cells. Nature. 489:101–108. 2012. View Article : Google Scholar : PubMed/NCBI
12	Mattick JS: Non-coding RNAs: The architects of eukaryotic complexity. EMBO Rep. 2:986–991. 2001. View Article : Google Scholar : PubMed/NCBI
13	Mattick JS and Gagen MJ: The evolution of controlled multitasked gene networks: The role of introns and other noncoding RNAs in the development of complex organisms. Mol Biol Evol. 18:1611–1630. 2001. View Article : Google Scholar : PubMed/NCBI
14	Tay Y, Rinn J and Pandolfi PP: The multilayered complexity of ceRNA crosstalk and competition. Nature. 505:344–352. 2014. View Article : Google Scholar : PubMed/NCBI
15	Gutschner T and Diederichs S: The hallmarks of cancer: A long non-coding RNA point of view. RNA Biol. 9:703–719. 2012. View Article : Google Scholar : PubMed/NCBI
16	Kasinski AL and Slack FJ: Epigenetics and genetics. MicroRNAs en route to the clinic: Progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 11:849–864. 2011. View Article : Google Scholar : PubMed/NCBI
17	Stahlhut C and Slack FJ: MicroRNAs and the cancer phenotype: Profiling, signatures and clinical implications. Genome Med. 5:111–122. 2013. View Article : Google Scholar
18	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
19	Dvinge H, Git A, Gräf S, Salmon-Divon M, Curtis C, Sottoriva A, Zhao Y, Hirst M, Armisen J, Miska EA, et al: The shaping and functional consequences of the microRNA landscape in breast cancer. Nature. 497:378–382. 2013. View Article : Google Scholar : PubMed/NCBI
20	Kim TM, Huang W, Park R, Park PJ and Johnson MD: A developmental taxonomy of glioblastoma defined and maintained by MicroRNAs. Cancer Res. 71:3387–3399. 2011. View Article : Google Scholar : PubMed/NCBI
21	Manterola L, Guruceaga E, Gállego Pérez-Larraya J, González-Huarriz M, Jauregui P, Tejada S, Diez-Valle R, Segura V, Samprón N, Barrena C, et al: A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool. Neuro-oncol. 16:520–527. 2014. View Article : Google Scholar : PubMed/NCBI
22	Tsai MC, Spitale RC and Chang HY: Long intergenic noncoding RNAs: New links in cancer progression. Cancer Res. 71:3–7. 2011. View Article : Google Scholar : PubMed/NCBI
23	Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
24	Wang F, Li X, Xie X, Zhao L and Chen W: UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion. FEBS Lett. 582:1919–1927. 2008. View Article : Google Scholar : PubMed/NCBI
25	Yang C, Li X, Wang Y, Zhao L and Chen W: Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells. Gene. 496:8–16. 2012. View Article : Google Scholar : PubMed/NCBI
26	Metzker ML: Sequencing technologies - the next generation. Nat Rev Genet. 11:31–46. 2010. View Article : Google Scholar
27	Buermans HP, Ariyurek Y, van Ommen G, den Dunnen JT and ‘t Hoen PA: New methods for next generation sequencing based microRNA expression profiling. BMC Genomics. 11:716–731. 2010. View Article : Google Scholar : PubMed/NCBI
28	Anselmo A, Flori L, Jaffrezic F, Rutigliano T, Cecere M, Cortes-Perez N, Lefèvre F, Rogel-Gaillard C and Giuffra E: Co-expression of host and viral microRNAs in porcine dendritic cells infected by the pseudorabies virus. PLoS One. 6:e173742011. View Article : Google Scholar : PubMed/NCBI
29	Stark MS, Tyagi S, Nancarrow DJ, Boyle GM, Cook AL, Whiteman DC, Parsons PG, Schmidt C, Sturm RA and Hayward NK: Characterization of the melanoma miRNAome by deep sequencing. PLoS One. 5:e96852010. View Article : Google Scholar : PubMed/NCBI
30	Li M, Liu Y, Wang T, Guan J, Luo Z, Chen H, Wang X, Chen L, Ma J, Mu Z, et al: Repertoire of porcine microRNAs in adult ovary and testis by deep sequencing. Int J Biol Sci. 7:1045–1055. 2011. View Article : Google Scholar : PubMed/NCBI
31	Wang R, Wang ZX, Yang JS, Pan X, De W and Chen LB: MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14). Oncogene. 30:2644–2658. 2011. View Article : Google Scholar : PubMed/NCBI
32	Guan Y, Mizoguchi M, Yoshimoto K, Hata N, Shono T, Suzuki SO, Araki Y, Kuga D, Nakamizo A, Amano T, et al: MiRNA-196 is upregulated in glioblastoma but not in anaplastic astrocytoma and has prognostic significance. Clin Cancer Res. 16:4289–4297. 2010. View Article : Google Scholar : PubMed/NCBI
33	Schimanski CC, Frerichs K, Rahman F, Berger M, Lang H, Galle PR, Moehler M and Gockel I: High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. World J Gastroenterol. 15:2089–2096. 2009. View Article : Google Scholar : PubMed/NCBI
34	Luthra R, Singh RR, Luthra MG, Li YX, Hannah C, Romans AM, Barkoh BA, Chen SS, Ensor J, Maru DM, et al: MicroRNA-196a targets annexin A1: A microRNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene. 27:6667–6678. 2008. View Article : Google Scholar : PubMed/NCBI
35	Sun M, Liu XH, Li JH, Yang JS, Zhang EB, Yin DD, Liu ZL, Zhou J, Ding Y, Li SQ, et al: MiR-196a is upregulated in gastric cancer and promotes cell proliferation by downregulating p27(kip1). Mol Cancer Ther. 11:842–852. 2012. View Article : Google Scholar : PubMed/NCBI