Identification of long-non coding RNA UCA1 as an oncogene in renal cell carcinoma

Li,Yifan; Wang,Tiantian; Li,Yuchi; Chen,Duqun; Yu,Zuhu; Jin,Lu; Ni,Liangchao; Yang,Shangqi; Mao,Xiangming; Gui,Yaoting; Lai,Yongqing

doi:10.3892/mmr.2016.4894

Identification of long-non coding RNA UCA1 as an oncogene in renal cell carcinoma

Authors:
- Yifan Li
- Tiantian Wang
- Yuchi Li
- Duqun Chen
- Zuhu Yu
- Lu Jin
- Liangchao Ni
- Shangqi Yang
- Xiangming Mao
- Yaoting Gui
- Yongqing Lai
View Affiliations

Affiliations: Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Department of Urology, Anhui Medical University, Hefei, Anhui 230032, P.R. China, The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
Published online on: February 16, 2016 https://doi.org/10.3892/mmr.2016.4894
Pages: 3326-3334

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

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, which is associated with poor prognosis and high recurrence. Long non‑coding RNAs (lncRNAs) have been reported to be dysregulated in cancer and to be important in the regulation of carcinogenesis, thus suggesting that this class of molecules may be used as biomarkers in cancer. The lncRNA urothelial carcinoma associated 1 (UCA1) has been observed to be upregulated and to function as an oncogene in certain types of cancer; however, the role of UCA1 in RCC remains to be elucidated. The present study aimed to determine the expression and function of UCA1 in RCC. Quantitative polymerase chain reaction (qPCR) was used to determine the expression levels of UCA1 in 46 paired RCC and adjacent normal tissue samples. Furthermore, qPCR was used to determine the expression levels of UCA1 in four RCC cell lines compared with the human embryonic kidney 293T cell line. The impact of UCA1 on cell migration, proliferation and apoptosis was investigated by wound scratch assay, MTT and flow cytometry, respectively. The results of the present study demonstrated that UCA1 expression levels were significantly increased in RCC tissues and cells, as compared with the controls. Ectopic expression and gene silencing of UCA1 in RCC cell lines exerted opposite effects on cellular proliferation, migration and apoptosis, and the results suggested that UCA1 may function as an oncogene in RCC. These results indicated that UCA1 may be considered as a promising biomarker for diagnosis, and a therapeutic target in RCC. Further research is required to elucidate the role and target genes of UCA1 in RCC.

View Figures

View References

1	Tavani A and La Vecchia C: Epidemiology of renal-cell carcinoma. J Nephrol. 10:93–106. 1997.PubMed/NCBI
2	National Cancer Institute: Surveillance, Epidemiology, and End Results Program. SEER stat fact sheets: Kidney and renal pelvis cancer. Available at: http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed 30, 2014.
3	Motzer RJ, Bander NH and Nanus DM: Renal-cell carcinoma. N Engl J Med. 335:865–875. 1996. View Article : Google Scholar : PubMed/NCBI
4	Cohen HT and McGovern FJ: Renal-cell carcinoma. N Engl J. 353:2477–2490. 2005. View Article : Google Scholar
5	Ridge CA, Pua BB and Madoff DC: Epidemiology and staging of renal cell carcinoma. Semin Intervent Radiol. 31:3–8. 2014. View Article : Google Scholar : PubMed/NCBI
6	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
7	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
8	Spizzo R, Almeida MI, Colombatti A and Calin GA: Long non-coding RNAs and cancer: A new frontier of translational research? Oncogene. 31:4577–4587. 2012. View Article : Google Scholar : PubMed/NCBI
9	Li X, Wu Z, Fu X and Han W: Long noncoding RNAs: Insights from biological features and functions to diseases. Med Res Rev. 33:517–553. 2013. View Article : Google Scholar
10	Takagi M, Absalon MJ, McLure KG and Kastan MB: Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell. 123:49–63. 2005. View Article : Google Scholar : PubMed/NCBI
11	Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, Laxman B, Asangani IA, Grasso CS, Kominsky HD, et al: Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol. 29:742–749. 2011. View Article : Google Scholar : PubMed/NCBI
12	Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, et al: Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res. 12:4851–4858. 2006. View Article : Google Scholar : PubMed/NCBI
13	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
14	Xie XJ, Li X, Wang F and Chen W: Cellular localization and tissue expression pattern of UCA1, a non-coding RNA. Nan Fang Yi Ke Da Xue Xue Bao. 30:57–60. 2010.In Chinese. PubMed/NCBI
15	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
16	Tsang WP, Wong TW, Cheung AH, Co CN and Kwok TT: Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR. RNA. 13:890–898. 2007. View Article : Google Scholar : PubMed/NCBI
17	Tian Y, Zhang X, Hao Y, Fang Z and He Y: Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma. Melanoma Res. 24:335–341. 2014. View Article : Google Scholar : PubMed/NCBI
18	Han Y, Yang YN, Yuan HH, Zhang TT, Sui H, Wei XL, Liu L, Huang P, Zhang WJ and Bai YX: UCA1, a long non-coding RNA up-regulated in colorectal cancer influences cell proliferation, apoptosis and cell cycle distribution. Pathology. 46:396–401. 2014. View Article : Google Scholar : PubMed/NCBI
19	Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M and Mo YY: Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis. 5:e10082014. View Article : Google Scholar : PubMed/NCBI
20	Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC cancer staging manual. 7th edition. Springer; New York, NY: pp. 479–89. 2010
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
22	Wang T, Yuan J, Feng N, Li Y, Lin Z, Jiang Z and Gui Y: Hsa-miR-1 downregulates long non-coding RNA urothelial cancer associated 1 in bladder cancer. Tumour Biol. 35:10075–10084. 2014. View Article : Google Scholar : PubMed/NCBI
23	Shi X, Sun M, Liu H, Yao Y and Song Y: Long non-coding RNAs: A new frontier in the study of human diseases. Cancer Lett. 339:159–166. 2013. View Article : Google Scholar : PubMed/NCBI
24	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
25	Martens-Uzunova ES, Böttcher R, Croce CM, Jenster G, Visakorpi T and Calin GA: Long noncoding RNA in prostate, bladder, and kidney cancer. Eur Urol. 65:1140–1151. 2014. View Article : Google Scholar : PubMed/NCBI
26	Li Z, Li X, Wu S, Xue M and Chen W: Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR-STAT3/microRNA143 pathway. Cancer Sci. 105:951–955. 2014. View Article : Google Scholar : PubMed/NCBI
27	Kumar PP, Emechebe U, Smith R, Franklin S, Moore B, Yandell M, Lessnick SL and Moon AM: Coordinated control of senescence by lncRNA and a novel T-box3 co-repressor complex. Elife. 3:e028052014. View Article : Google Scholar
28	Yang L, Froberg JE and Lee JT: Long noncoding RNAs: Fresh perspectives into the RNA world. Trends Biochem Sci. 39:35–43. 2014. View Article : Google Scholar :
29	Wang Y, Chen W, Yang C, Wu W, Wu S, Qin X and Li X: Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer. Int J Oncol. 41:276–284. 2012.PubMed/NCBI
30	Xue M, Li X, Wu W, Zhang S, Wu S, Li Z and Chen W: Upregulation of long non-coding RNA urothelial carcinoma associated 1 by CCAAT/enhancer binding protein α contributes to bladder cancer cell growth and reduced apoptosis. Oncol Rep. 31:1993–2000. 2014.PubMed/NCBI
31	Xue M, Li X, Li Z and Chen W: Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumour Biol. 35:6901–6912. 2014. View Article : Google Scholar : PubMed/NCBI
32	Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F and Liu Y: Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling. FEBS J. 281:1750–1758. 2014. View Article : Google Scholar : PubMed/NCBI
33	Wu W, Zhang S, Li X, Xue M, Cao S and Chen W: Ets-2 regulates cell apoptosis via the Akt pathway, through the regulation of urothelial cancer associated 1, a long non-coding RNA, in bladder cancer cells. PLoS One. 820132013.
34	Cairns RA, Harris IS and Mak TW: Regulation of cancer cell metabolism. Nat Rev Cancer. 11:85–95. 2011. View Article : Google Scholar : PubMed/NCBI
35	Srivastava AK, Singh PK, Rath SK, Dalela D, Goel MM and Bhatt ML: Appraisal of diagnostic ability of UCA1 as a biomarker of carcinoma of the urinary bladder. Tumour Biol. 35:11435–11442. 2014. View Article : Google Scholar : PubMed/NCBI
36	Zhang Z, Hao H, Zhang CJ, Yang XY, He Q and Lin J: Evaluation of novel gene UCA1 as a tumor biomarker for the detection of bladder cancer. Zhonghua Yi Xue Za Zhi. 92:384–387. 2012.In Chinese. PubMed/NCBI