Skip to main content

Advertisement

Log in

RETRACTED ARTICLE: Downregulation of long non-coding RNA TUG1 suppresses tumor growth by promoting ubiquitination of MET in diffuse large B-cell lymphoma

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

This article was retracted on 13 October 2022

This article has been updated

Abstract

Long non-coding RNAs (lncRNAs) can modulate gene expression through different mechanisms, but the fundamental molecular mechanism between lncRNAs and MET protein in diffuse large B-cell lymphoma (DLBCL) was poorly understood. The expression of lncRNA TUG1 and MET in DLBCL tissues and cell lines was determined by quantitative real-time PCR and western blotting. Cell proliferation, invasion and apoptosis were determined by cell counting kit-8 assay, transwell assay and flow cytometer. The animal xenograft model was established by the injection of DLBCL cells carrying si-TUG1. The expression of TUG1 and MET was upregulated in DLBCL tissues and cells. We demonstrated that MET was altered in the TUG1 knockdown DLBCL cells, and confirmed the interaction between TUG1 and MET by RNA pull-down and RNA immunoprecipitation. Furthermore, knockdown of TUG1 reduced MET protein level by promoting ubiquitination, and suppressed tumor growth in vitro and in vivo. Our findings demonstrated that TUG1 exerted its oncogenic function in DLBCL by inhibiting the ubiquitination and the subsequent degradation of MET. Knockdown of TUG1 through MET downregulation suppressed DLBCL cell proliferation and tumor growth.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Change history

References

  1. Green TM, Young KH, Visco C et al (2012) Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol 30(28):3460–3467

    Article  CAS  Google Scholar 

  2. Xu-Monette ZY, Wu L, Visco C et al (2013) Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with Rituximab-CHOP: a report from an international DLBCL Rituximab-CHOP consortium program study. Clin Lymphoma Myeloma Leukemia 13:S382

    Article  Google Scholar 

  3. Castillo JJ, Winer ES, Olszewski AJ (2014) Sites of extranodal involvement are prognostic in patients with diffuse large B-cell lymphoma in the rituximab era: an analysis of the Surveillance, Epidemiology and End Results database. Am J Hematol 89(3):310–314

    Article  CAS  Google Scholar 

  4. Saito B, Shiozawa E, Usui T et al (2007) Rituximab with chemotherapy improves survival of non-germinal center type untreated diffuse large B-cell lymphoma. Leukemia 21(12):2563–2566

    Article  CAS  Google Scholar 

  5. Sehn LH, Gascoyne RD (2015) Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood 125(1):22

    Article  CAS  Google Scholar 

  6. Bottaro DP, Rubin JS, Faletto DL et al (1991) Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251(4995):802

    Article  CAS  Google Scholar 

  7. Livio T, Paolo MC (2002) Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer 2(4):289–300

    Article  Google Scholar 

  8. Renzo MF, Di Olivero M, Ferro S et al (1992) Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 7(12):2549–2553

    PubMed  Google Scholar 

  9. Humphrey PA, Zhu X, Zarnegar R et al (1995) Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am J Pathol 147(2):386

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Yonemura Y, Kaji M, Hirono Y et al (1996) Correlation between overexpression of c-met gene and the progression of gastric cancer. Int J Oncol 8(3):555

    CAS  PubMed  Google Scholar 

  11. Mahtouk K, Tjin EPM, Spaargaren M, Pals ST (2010) The HGF/MET pathway as target for the treatment of multiple myeloma and B-cell lymphomas. BBA—Rev Cancer 1806(2):208–219

    CAS  Google Scholar 

  12. Kawano R, Ohshima K, Karube K et al (2004) Prognostic significance of hepatocyte growth factor and c-MET expression in patients with diffuse large B-cell lymphoma. Br J Haematol 127(3):305

    Article  CAS  Google Scholar 

  13. Kang Won J, Jeong Eun L, Sun Young K et al (2011) The C-terminus of Hsp70-interacting protein promotes Met receptor degradation. J Thoracic Oncol 6(4):679–687

    Article  Google Scholar 

  14. Caley DP, Pink RC, Trujillano D, Carter DR (2010) Long noncoding RNAs, chromatin, and development. Sci World J 10(1):90

    Article  CAS  Google Scholar 

  15. Zhou YX, Mao LW, Wang YL (2017) Increased LncRNA PVT-1 is associated with tumor proliferation and predicts poor prognosis in cervical cancer. Clin Surg Res Commun 1(1):10–17

    Article  Google Scholar 

  16. Wang Y, Zhang M, Xu H et al (2017) Discovery and validation of the tumor-suppressive function of long noncoding RNA PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK/ERK signaling pathway. Oncotarget 8(42):72182–72196

    Article  Google Scholar 

  17. Deng L, Jiang L, Tseng K-F et al (2018) Aberrant NEAT1_1 expression may be a predictive marker of poor prognosis in diffuse large B cell lymphoma. Cancer Biomark 23(2):157–164

    Article  CAS  Google Scholar 

  18. Dousti F, Shahrisa A, Ansari H et al (2018) Long non-coding RNAs expression levels in diffuse large B-cell lymphoma: an in silico analysis. Pathology—Res Pract 214(9):1462–1466

    Article  CAS  Google Scholar 

  19. Eis PS, Tam W, Sun L et al (2005) Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA 102(10):3627–3632

    Article  CAS  Google Scholar 

  20. Wang Z-Q, He C-Y, Hu L et al (2017) Long noncoding RNA UCA1 promotes tumour metastasis by inducing GRK2 degradation in gastric cancer. Cancer Lett 408:10–21

    Article  CAS  Google Scholar 

  21. Wang K, Long B, Zhou L-Y et al (2014) CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun 5:3596

    Article  Google Scholar 

  22. Kang WJ, Lee JE, Sun YK et al (2011) The C-terminus of Hsp70-Interacting Protein Promotes Met Receptor Degradation. J Thoracic Oncol 6(4):679–687

    Article  Google Scholar 

  23. Zhang J, Grubor V, Love CL et al (2013) Genetic heterogeneity of diffuse large B-cell lymphoma. Proc Natl Acad Sci USA 110(4):1398–1403

    Article  CAS  Google Scholar 

  24. Youtao X, Jie W, Mantang Q et al (2015) Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma. Tumor Biol 36(3):1643–1651

    Article  Google Scholar 

  25. Jiemei T, Kaifeng Q, Mingyi L, Ying L (2016) Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells. FEBS Lett 589:3175–3181

    Google Scholar 

  26. Heng C, Yixue X, Ping W et al (2015) The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144. Oncotarget 6(23):19759–19779

    Article  Google Scholar 

  27. Lin YH, Wu MH, Huang YH et al (2017) Taurine upregulated gene 1 functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma. Hepatology 67(1):188–203

    Article  Google Scholar 

  28. Ma B, Li M, Zhang L et al (2015) Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma. Tumor Biol 37(4):1–11

    Google Scholar 

  29. Sun J, Ding C, Yang Z et al (2016) The long non-coding RNA TUG1 indicates a poor prognosis for colorectal cancer and promotes metastasis by affecting epithelial-mesenchymal transition. J Transl Med 14(1):42

    Article  Google Scholar 

  30. Tjin EPM, Groen RWJ, Vogelzang I et al (2006) Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma. Blood 107(2):760

    Article  CAS  Google Scholar 

  31. Shahab U, Hussain AR, Maqbool A et al (2010) Inhibition of c-MET is a potential therapeutic strategy for treatment of diffuse large B-cell lymphoma. Lab Invest 90(9):1346–1356

    Article  Google Scholar 

  32. Uddin S, Hussain AR, Ahmed M et al (2010) Inhibition of fatty acid synthase suppresses c-Met receptor kinase and induces apoptosis in diffuse large B-cell lymphoma. Mol Cancer Ther 9(5):1244–1255

    Article  CAS  Google Scholar 

  33. Jia YJ, Liu ZB, Wang WG et al (2017) HDAC6 regulates microRNA-27b that suppresses proliferation, promotes apoptosis and target MET in diffuse large B-cell lymphoma. Leukemia. 32(3):703

    Article  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81871263, 81770223, 81500097, and 81500088).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kailin Xu.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Institute Research Medical Ethics Committee of The Affiliated Hospital of Xuzhou Medical University.

Informed consent

All the patients were participating in this study with written informed consent.

Research involving human and animal participants

All animal experiments were proved by the Institute Research Medical Ethics Committee of Xuzhou Medical University, and all animals-treatment operations were executed according to the Xuzhou Medical University Ethical Guidelines for Animal Experiment.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s11010-022-04566-2

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, H., Yan, Z., Wang, X. et al. RETRACTED ARTICLE: Downregulation of long non-coding RNA TUG1 suppresses tumor growth by promoting ubiquitination of MET in diffuse large B-cell lymphoma. Mol Cell Biochem 461, 47–56 (2019). https://doi.org/10.1007/s11010-019-03588-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-019-03588-7

Keywords

Navigation