Skip to main content

Advertisement

SpringerLink
Log in

LncRNA CCAT1 inhibits cell apoptosis of renal cell carcinoma through up-regulation of Livin protein

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

This study was to investigate the involvement of long non-coding RNA (lncRNA) colon cancer-associated transcript-1 (CCAT1) in renal cell carcinoma (RCC) and to further uncover its underlying mechanism. In this study, the expression of CCAT1 and Livin of RCC tissues or cells was determined using qRT-PCR (quantitative real-time PCR) and western blot, respectively. RNA pulldown and RIP (RNA-Binding Protein Immunoprecipitation) assays were performed to examine the sequence interaction between CCAT1 and Livin. The viability and apoptosis of RCC cells was assessed by MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and TUNEL (TdT-mediated dUTP nick end labeling) assays, respectively. Mice of tumor animal models were established to observe the effect of CCAT1 on RCC tumor growth. The relative expression of CCAT1 in RCC tissues and cell lines was obviously higher than that of the control. CCAT1 knockdown could reduce cell viability and increase the apoptosis of RCC cells in vitro. Furthermore, Livin was significantly inhibited by CCAT1 silencing; RNA pulldown and RIP assays showed that CCAT1 was physically associated with Livin protein. Moreover, Livin overexpression not only significantly inhibited RCC cell apoptosis and increased cell viability, but completely reversed the si-CCAT1-mediated repression of cell viability. More importantly, CCAT1 silencing could inhibit the growth of RCC in vivo that was accompanied by the reduction of Livin in RCC tissues. CCAT1 inhibits RCC cell apoptosis and increases cell viability through up-regulation of Livin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Seliger B, Menig M, Lichtenfels R, Atkins D, Bukur J, Halder TM, Kersten M, Harder A, Ackermann A, Beck J (2003) Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy. Proteomics 3:979–990

    Article  CAS  PubMed  Google Scholar 

  2. Bracarda S (2009) Metastatic renal cell carcinoma: pathogenesis and the current medical landscape. Eur Urol Suppl 8:787–792

    Article  Google Scholar 

  3. Ip JY, Nakagawa S (2012) Long non-coding RNAs in nuclear bodies. Dev Growth Differ 54:44–54. doi:10.1111/j.1440-169X.2011.01303.x

    Article  CAS  PubMed  Google Scholar 

  4. Lawson J, Singh R, Hultner M, Ariyur K, Martin L (2012) Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene 31:4577–4587

    Article  Google Scholar 

  5. Shao K, Shi T, Yang Y, Wang X, Da X, Zhou P (2016) Highly expressed lncRNA CRNDE promotes cell proliferation through Wnt/β-catenin signaling in renal cell carcinoma. Tumor Biol 37:15997−16004

    Article  CAS  Google Scholar 

  6. Xiong J, Liu Y, Luo S, Jiang L, Zeng Y, Chen Z, Shi X, Lv B, Tang W (2017) High expression of the long non-coding RNA HEIRCC promotes Renal Cell Carcinoma metastasis by inducing epithelial-mesenchymal transition. Oncotarget 8:6555–6563. doi:10.18632/oncotarget.14149

    PubMed  Google Scholar 

  7. Chen S, Ma P, Zhao Y, Li B, Jiang S, Xiong H, Wang Z, Wang H, Jin X, Liu C (2016) Biological function and mechanism of MALAT-1 in renal cell carcinoma proliferation and apoptosis: role of the MALAT-1-Livin protein interaction. J Physiol Sci. doi:10.1007/s12576-016-0486-8

    PubMed  Google Scholar 

  8. Meng Z, Wei L, Huang Y, Shi J, Xun W (2016) Downregulation of the long noncoding RNA TUG1 inhibits the proliferation, migration, invasion and promotes apoptosis of renal cell carcinoma. J Mol Histol 47:421–428

    Article  Google Scholar 

  9. Nissan A, Stojadinovic A, Mitrani-Rosenbaum S, Halle D, Grinbaum R, Roistacher M, Bochem A, Dayanc BE, Ritter G, Gomceli I, Bostanci EB, Akoglu M, Chen YT, Old LJ, Gure AO (2012) Colon cancer associated transcript-1: a novel RNA expressed in malignant and pre-malignant human tissues. Int J Cancer 130:1598–1606. doi:10.1002/ijc.26170

    Article  CAS  PubMed  Google Scholar 

  10. He X, Tan X, Wang X, Jin H, Liu L, Ma L, Yu H, Fan Z (2014) C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion. Tumor Biol 35:12181–12188

    Article  CAS  Google Scholar 

  11. Xin Y, Li Z, Shen J, Chan MT, Wu WK (2016) CCAT1: a pivotal oncogenic long non-coding RNA in human cancers. Cell Prolif 49:255–260

    Article  CAS  PubMed  Google Scholar 

  12. Salvesen GS, Duckett CS (2002) IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol 3:401–410. doi:10.1038/nrm830

    Article  CAS  PubMed  Google Scholar 

  13. Franklin MC, Kadkhodayan S, Ackerly H, Alexandru D, Distefano MD, Elliott LO, Flygare JA, Mausisa G, Okawa DC, Ong D (2003) Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP). Biochemistry 42:8223–8231

    Article  CAS  PubMed  Google Scholar 

  14. Altieri B, Sbiera S, Della Casa S, Weigand I, Wild V, Steinhauer S, Fadda G, Kocot A, Bekteshi M, Mambretti EM, Rosenwald A, Pontecorvi A, Fassnacht M, Ronchi CL (2017) Livin/BIRC7 expression as malignancy marker in adrenocortical tumors. Oncotarget 8:9323–9338. doi:10.18632/oncotarget.14067

    PubMed  Google Scholar 

  15. Yin L, Liu S, Li C, Ding S, Bi D, Niu Z, Han L, Li W, Gao D, Liu Z (2016) CYLD downregulates Livin and synergistically improves gemcitabine chemosensitivity and decreases migratory/invasive potential in bladder cancer: the effect is autophagy-associated. Tumor Biol 37:1–12

    CAS  Google Scholar 

  16. Yang G, Cao X, Wang D, Wei S, Sun H, Bing H, Cui J, Liu B (2016) Overexpression of Livin promotes migration and invasion of colorectal cancer cells by induction of epithelial–mesenchymal transition via NF-κB activation. Acta Geosicientia Sin 25:579–582

    Google Scholar 

  17. Liu C, Wu X, Luo C, Hu Z, Yin Z, He Y, Du H, Zhang W, Jiang Q, Lin Y (2010) Antisense oligonucleotide targeting Livin induces apoptosis of human bladder cancer cell via a mechanism involving caspase 3. J Exp Clin Cancer Res 29:63. doi:10.1186/1756-9966-29-63

    Article  PubMed  Google Scholar 

  18. Kempkensteffen C, Hinz S, Christoph F, Krause H, Koellermann J, Magheli A, Schrader M, Schostak M, Miller K, Weikert S (2007) Expression of the apoptosis inhibitor Livin in renal cell carcinomas: correlations with pathology and outcome. Tumour Biol 28:132–138

    Article  CAS  PubMed  Google Scholar 

  19. Liu B, Han M, Wen JK, Wang L (2007) Livin/ML-IAP as a new target for cancer treatment. Cancer Lett 250:168–176

    Article  CAS  PubMed  Google Scholar 

  20. Wang Z, Shuai L, Ding K, Ding S, Li C, Lu J, Gao D, Tong Z, Bi D (2016) Silencing Livin induces apoptotic and autophagic cell death, increasing chemotherapeutic sensitivity to cisplatin of renal carcinoma cells. Tumor Biol 37:15133–15143

    Article  CAS  Google Scholar 

  21. Wagener N, Crnkovićmertens I, Vetter C, Machergöppinger S, Bedke J, Gröne EF, Zentgraf H, Pritsch M, Hoppeseyler K, Buse S (2007) Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney. Br J Cancer 97:1271–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Crnkovićmertens I, Wagener N, Semzow J, Gröne EF, Haferkamp A, Hohenfellner M, Butz K, Hoppeseyler F (2007) Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis. Cell Mol Life Sci Cmls 64:1137–1144

    Article  Google Scholar 

Download references

Acknowledgements

The study was supported by Provincial Natural Science Foundation of Chongqing (NO. cstc2013jcyjA0437). Special thanks to Professor Liu Chuan for his technical guidance and fund support.

Author information

Authors and Affiliations

  1. Department of Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, 9677# Olympic Sports Centre Middle Road, Jinan, 250014, Shandong, People’s Republic of China

    Shaoan Chen, Xiude Chen, Yuzhu Xiang, Tengteng Wang, Xiangbin Ren & Xunbo Jin

  2. Department of Urology, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Lu, Chongqing, 400010, People’s Republic of China

    Pengpeng Ma, Dawei Zhu & Chuan Liu

  3. School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan, 250012, People’s Republic of China

    Bin Li

Authors
  1. Shaoan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pengpeng Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dawei Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiude Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuzhu Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tengteng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiangbin Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xunbo Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chuan Liu or Xunbo Jin.

Ethics declarations

Conflict of interest

All authors declare that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Ma, P., Li, B. et al. LncRNA CCAT1 inhibits cell apoptosis of renal cell carcinoma through up-regulation of Livin protein. Mol Cell Biochem 434, 135–142 (2017). https://doi.org/10.1007/s11010-017-3043-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-017-3043-8

Keywords

Search

Navigation