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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Change history
01 July 2020
In the original article, we realized that an error occurred when we grouped the separate photos to generate the combined Figure 4 The same image was accidentally pasted twice in one figure, while we were not fully aware of the error at that time. We immediately reviewed the original data again and made sure that no changes need to be made in other parts of the paper. We are sure that the published manuscript was published without prior knowledge of the error and that it does not alter the conclusions of the study.
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
References
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)
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
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
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)
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)
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)
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)
Motzer RJ, Bander NH, Nanus DM (1996) Medical progress: renal-cell carcinoma. N Engl J Med. doi:10.1056/NEJM199609193351207
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)
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)
Sigurdson ER (2013) NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw: JNCCN 11:58–77
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)
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)
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
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
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
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
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).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None declared.
Additional information
Meng Zhang, Wei Lu and Yiqiang Huang have contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Zhang, M., Lu, W., Huang, Y. et al. Downregulation of the long noncoding RNA TUG1 inhibits the proliferation, migration, invasion and promotes apoptosis of renal cell carcinoma. J Mol Hist 47, 421–428 (2016). https://doi.org/10.1007/s10735-016-9683-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-016-9683-2