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Journal of Molecular Histology

, Volume 47, Issue 4, pp 421–428 | Cite as

Downregulation of the long noncoding RNA TUG1 inhibits the proliferation, migration, invasion and promotes apoptosis of renal cell carcinoma

  • Meng Zhang
  • Wei Lu
  • Yiqiang Huang
  • Jizhou Shi
  • Xun Wu
  • Xiaolong Zhang
  • Runze Jiang
  • Zhiming Cai
  • Song WuEmail author
Original Paper

Abstract

Long non-coding RNAs, a newly discovered category of noncoding genes, play a leading role in various biological processes, including tumorigenesis. In our study, we aimed to examine the TUG1 expression, and explore the influence of TUG1 silencing on cell proliferation and apoptosis in renal cell carcinoma (RCC) cell lines. The TUG1 expression level was detected using quantitative real-time PCR reverse transcription-polymerase chain reaction in 40 paired clear cell renal cell carcinoma (ccRCC) and adjacent paired normal tissues, as well as four RCC cell lines and one normal human proximal tubule epithelial cell line HK-2. Small interfering RNA was applied to suppress the TUG1 expression in RCC cell lines (A489 and A704). In vitro assays were conducted to further deliberate its potential functions in RCC progression. The relative TUG1 expression was significantly higher in ccRCC tissues compared to the adjacent normal renal tissues. In addition, higher TUG1 expression was equally detected in RCC cell lines (particularly in A498 and A704) compared to HK-2. The ccRCC specimens with higher TUG1 expression had a higher Fuhrman grade and larger tumor size than those with lower TUG1 expression. In vitro assays results suggested that knockdown of TUG1 suppressed RCC cells migration, invasion and proliferation, while the apoptosis process was activated. Our results indicate that TUG1 is identified as a novel oncogene in the morbid state of RCC, which potentially acts as a therapeutic target/biomarker in RCC.

Graphical Abstract

The graphic abstract of the present work.

Keywords

TUG1 Renal cell carcinoma siRNA–TUG1 Biomarker 

Abbreviations

LncRNA

Long non-coding RNA

TUG1

Taurine upregulated gene 1

RCC

Renal cell carcinoma

RT-PCR

Reverse-transcription-polymerase chain reaction

siRNA

Small interfering RNA

CCAT2

Colon cancer associated transcript 2

NSCLC

Non-small cell lung carcinoma

CCK8

Cell Counting Kit-8

IBM

International Business Machines Corporation

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

AJCC

American Joint Committee on Cancer

ESCC

Esophageal squamous cell carcinoma

HOXB7

Homeobox B7

Notes

Acknowledgments

Conceived and designed the study: S. W. and Z. C. Execution and performed the experiments: M. Z., W. L. and Y. H. Analyzed and interpreted the data: M. Z., Y. H. and W. L. Contributed materials: M. Z. and Y. H. Drafted the manuscript: M. Z., W. L. and Y. H. Critically revised the manuscript for important intellectual content: S. W. and Z. C.

Funding

This work was supported by the Young Scientists Fund of the National Natural Science Foundation of China (81502207, 81201579 and 81301740), Shenzhen Basic Research Project (JCYJ20130401114928183; JCYJ20140416180323426), Shenzhen Knowledge Innovation Project (JCYJ20130401114715714), the Project of Science and Technology of Shenzhen (Technological Innovation Project: No. CXZZ20120614154434310) and the Plan of the Construction of Innovative Environment in Shenzhen (Key Laboratory: No.ZDSY20130531165409949).

Compliance with ethical standards

Conflict of interest

None declared.

Supplementary material

10735_2016_9683_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 15 kb)

References

  1. Cabili MN, Trapnell C, Goff L, Koziol M, Tazonvega B, Regev A, Rinn JL (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25:1915–1927. doi: 10.1101/gad.17446611 (Epub 2011 Sep 2) CrossRefPubMedPubMedCentralGoogle Scholar
  2. Cao W-J, Wu H-L, He B-S, Zhang Y-S, Zhang Z-Y (2013) Analysis of long non-coding RNA expression profiles in gastric cancer. World J Gastroenterol 19:3658–3664. doi: 10.3748/wjg.v19.i23.3658 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–1789. doi: 10.1101/gr.132159.111 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Han Y, Liu Y, Gui Y, Cai Z (2013) Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder. J Surg Oncol 107:555–559. doi: 10.1002/jso.23264 (Epub 2012 Sep 7) CrossRefPubMedGoogle Scholar
  5. Johnson R (2012) Long non-coding RNAs in Huntington’s disease neurodegeneration. Neurobiol Dis 46:245–254. doi: 10.1016/j.nbd.2011.12.006 (Epub 2011 Dec 14) CrossRefPubMedGoogle Scholar
  6. Lai C-Y, Xu Y, Yu G-S, Wu X, Li Y-F, Pan B, Heng B-L, Xue Y-J, Su Z-X (2016) Engrailed-2 might play an anti-oncogenic role in clear-cell renal cell carcinoma. J Mol Histol. doi: 10.1007/s10735-016-9665-4 (Epub 2016 Mar 7) PubMedGoogle Scholar
  7. Mitchell G, Ido A, Manuel G, Courtney F, Lin MF, David F, Maite H, Or Z, Carey BW, Cassady JP (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227. doi: 10.1038/nature07672 (Epub 2009 Feb 1) CrossRefGoogle Scholar
  8. Motzer RJ, Bander NH, Nanus DM (1996) Medical progress: renal-cell carcinoma. N Engl J Med. doi: 10.1056/NEJM199609193351207 PubMedGoogle Scholar
  9. Rini BI, Campbell SC, Escudier B (2009) Renal cell carcinoma, vol 20. Humana Press, Clifton, pp 300–306. doi: 10.1016/S0140-6736(09)60229-4 (Epub 2009 Mar 5) Google Scholar
  10. Shi X, Jiang J, Ye X, Liu Y, Wu Q, Lu W (2014) Prognostic prediction and diagnostic role of intercellular adhesion molecule-1 (ICAM1) expression in clear cell renal cell carcinoma. J Mol Histol 45:427–434. doi: 10.1007/s10735-014-9568-1 (Epub 2014 Feb 18) CrossRefPubMedGoogle Scholar
  11. Sigurdson ER (2013) NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw: JNCCN 11:58–77Google Scholar
  12. Xu Y, Wang J, Qiu M, Xu L, Li M, Jiang F, Yin R, Xu L (2015) Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma. Tumour Biol 36:1643–1651. doi: 10.1007/s13277-014-2763-6 (Epub 2014 Oct 31) CrossRefPubMedGoogle Scholar
  13. Xun W, Lin Y, Shi L, Yi H, Lai C, Wang Y, Meng Z, Wang S, Heng B, Yu G (2015) Upregulation of centromere protein H is associated with progression of renal cell carcinoma. J Mol Histol 46:377–385. doi: 10.1007/s10735-015-9635-2 (Epub 2015 Aug 7) CrossRefGoogle Scholar
  14. Yang Y (2012) A novel fumarate hydratase-deficient HLRCC kidney cancer cell line, UOK268: a model of the Warburg effect in cancer. Cancer Genet 205:377–390. doi: 10.1016/j.cancergen.2012.05.001 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Young TL, Matsuda T, Cepko CL (2005) The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol 15:501–512. doi: 10.1016/j.cub.2005.02.027 CrossRefPubMedGoogle Scholar
  16. Zhang Q, Geng PL, Yin P, Wang XL, Jia JP, Yao J (2013) Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. Asian Pac J Cancer Prev: APJCP 14:2311–2315. doi: 10.7314/APJCP.2013.14.4.2311 CrossRefPubMedGoogle Scholar
  17. Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, Han L, Xia R, Wang KM, Yang JS, De W, Shu YQ, Wang ZX (2014) P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis 5:e1243. doi: 10.1038/cddis.2014.201 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Meng Zhang
    • 1
    • 2
  • Wei Lu
    • 1
    • 2
  • Yiqiang Huang
    • 3
  • Jizhou Shi
    • 4
  • Xun Wu
    • 2
  • Xiaolong Zhang
    • 2
  • Runze Jiang
    • 2
  • Zhiming Cai
    • 1
  • Song Wu
    • 2
    Email author
  1. 1.Graduate School of Anhui Medical UniversityHefeiChina
  2. 2.Department of Urology, Shenzhen Luohu People’s HospitalShenzhen UniversityShenzhenChina
  3. 3.Department of UrologyZhujiang Hospital of Southern Medical UniversityGuangzhouChina
  4. 4.Department of General SurgeryShengli Oilfield Central HospitalDongyingChina

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