Skip to main content
SpringerLink
Log in

Negative feedback of miR-29 family TET1 involves in hepatocellular cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 24 January 2015

Abstract

Primary hepatocellular carcinoma (HCC) is the most common form of liver cancer and is one of the most common malignancies worldwide. Tumor suppressor gene silencing through DNA methylation contributes to cancer formation. The ten–eleven translocations (TET) family of α-ketogluta-rate-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine to 5-hydroxymethyl-cytosine, 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. MicroRNAs are an abundant class of 17–25 nucleotides small noncoding RNAs, identified as important regulators of many diverse biological processes. In this study, we showed that TET1 expression was obviously reduced in the majority of examined HCC tissues. And we further investigated the expression and functional involvement of TET1 in proliferation, migration and invasion, and determined that TET1 may function as a tumor suppressor. MiR-29b was proved to inhibit metastasis through the targeting of TET1, indicating that downregulation of miR-29 may involve in HCC carcinogenesis and progression through potentiation of TET1 expression. Thus, we elucidated the roles of feedback of miR-29-TET1 downregulation in HCC development and suggested a potential target in identification of the prognosis and application of cancer therapy for HCC patients.

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
Fig. 6

Similar content being viewed by others

Abbreviations

HCC:

Primary hepatocellular carcinoma

TET:

Ten–eleven translocation

α-KG:

α-Ketogluta-rate

5mC:

5-Methylcytosine

5hmC:

5-Hydroxymethyl-cytosine

miRNAs:

MicroRNAs

DMEM:

Dulbecco’s modified Eagle’s medium

HH:

Human hepatocytes

TCL1:

T cell leukemia/lymphoma 1

Mcl-1:

Myeloid cell leukemia sequence 1

CDC42:

Cell division cycle 42

EGFP:

Enhanced green fluorescent protein

FBS:

Fatal bovine serum

References

  1. Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. Hepatology. 2008;48(6):2047–63.

    Article  CAS  PubMed  Google Scholar 

  2. Villanueva A, Toffanin S, Llovet JM. Linking molecular classification of hepatocellular carcinoma and personalized medicine: preliminary steps. Curr Opin Oncol. 2008;20(4):444–53.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia. 2003;17(3):637–41.

    Article  CAS  PubMed  Google Scholar 

  4. Hsu CH, Peng KL, Kang ML, Chen YR, Yang YC, Tsai CH, et al. TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases. Cell Rep. 2012;2(3):568–79.

    Article  CAS  PubMed  Google Scholar 

  5. Albano F, Anelli L, Zagaria A, Coccaro N, Minervini A, Rossi AR, et al. Decreased TET2 gene expression during chronic myeloid leukemia progression. Leuk Res. 2011;35(11):e220–2.

    Article  CAS  PubMed  Google Scholar 

  6. Euba B, Vizmanos JL, Garcia-Granero M, Aranaz P, Hurtado C, Migueliz I, et al. A meta-analysis of TET2 mutations shows a distinct distribution pattern in de novo acute myeloid leukemia and chronic myelomonocytic leukemia. Leuk Lymphoma. 2012;53(6):1230–3.

    Article  CAS  PubMed  Google Scholar 

  7. Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature. 2010;468(7325):839–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol. 2007;23:175–205.

    Article  CAS  PubMed  Google Scholar 

  10. Spizzo R, Nicoloso MS, Croce CM, Calin GA. SnapShot: MicroRNAs in Cancer. Cell. 2009;137(3):586.

    Article  CAS  PubMed  Google Scholar 

  11. Garzon R, Calin GA, Croce CM. MicroRNAs in Cancer. Annu Rev Med. 2009;60:167–79.

    Article  CAS  PubMed  Google Scholar 

  12. Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009;361(15):1437–47.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Xiong Y, Fang JH, Yun JP, Yang J, Zhang Y, Jia WH, et al. Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 2010;51(3):836–45.

    CAS  PubMed  Google Scholar 

  14. Braconi C, Valeri N, Gasparini P, Huang N, Taccioli C, Nuovo G, et al. Hepatitis C virus proteins modulate microRNA expression and chemosensitivity in malignant hepatocytes. Clin Cancer Res. 2010;16(3):957–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Pineau P, Volinia S, McJunkin K, Marchio A, Battiston C, Terris B, et al. miR-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci USA. 2010;107(1):264–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Jiang J, Gusev Y, Aderca I, Mettler TA, Nagorney DM, Brackett DJ, et al. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res. 2008;14(2):419–27.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647–58.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu CG, et al. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 2007;67(13):6092–9.

    Article  CAS  PubMed  Google Scholar 

  19. Wong QW, Lung RW, Law PT, Lai PB, Chan KY, To KF, et al. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology. 2008;135(1):257–69.

    Article  CAS  PubMed  Google Scholar 

  20. Wang Y, Lee AT, Ma JZ, Wang J, Ren J, Yang Y, et al. Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target. J Biol Chem. 2008;283(19):13205–15.

    Article  CAS  PubMed  Google Scholar 

  21. Su H, Yang JR, Xu T, Huang J, Xu L, Yuan Y, et al. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 2009;69(3):1135–42.

    Article  CAS  PubMed  Google Scholar 

  22. Xu T, Zhu Y, Xiong Y, Ge YY, Yun JP, Zhuang SM. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology. 2009;50(1):113–21.

    Article  CAS  PubMed  Google Scholar 

  23. Law PT, Wong N. Emerging roles of microRNA in the intracellular signaling networks of hepatocellular carcinoma. J Gastroenterol Hepatol. 2011;26(3):437–49.

    Article  CAS  PubMed  Google Scholar 

  24. Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, et al. NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell. 2008;14(5):369–81.

    Article  CAS  PubMed  Google Scholar 

  25. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA. 2007;104(40):15805–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Mott JL, Kobayashi S, Bronk SF, Gores GJ. mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 2007;26(42):6133–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, et al. microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. 2011;30(47):4750–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, et al. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006;66(24):11590–3.

    Article  CAS  PubMed  Google Scholar 

  29. Park SY, Lee JH, Ha M, Nam JW, Kim VN. miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol. 2009;16(1):23–9.

    Article  CAS  PubMed  Google Scholar 

  30. Ozaki I, Mizuta T, Zhao G, Yotsumoto H, Hara T, Kajihara S, et al. Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma. Cancer Res. 2000;60(22):6519–25.

    CAS  PubMed  Google Scholar 

  31. Jiang Y, Xu W, Lu J, He F, Yang X. Invasiveness of hepatocellular carcinoma cell lines: contribution of hepatocyte growth factor, c-met, and transcription factor Ets-1. Biochem Biophys Res Commun. 2001;286(5):1123–30.

    Article  CAS  PubMed  Google Scholar 

  32. Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, et al. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 2009;113(25):6411–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Cedar H, Bergman Y. Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009;10(5):295–304.

    Article  CAS  PubMed  Google Scholar 

  34. Bestor T, Laudano A, Mattaliano R, Ingram V. Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol. 1988;203(4):971–83.

    Article  CAS  PubMed  Google Scholar 

  35. Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH. Dnmt3L and the establishment of maternal genomic imprints. Science. 2001;294(5551):2536–9.

    Article  PubMed  Google Scholar 

  36. Loenarz C, Schofield CJ. Oxygenase catalyzed 5-methylcytosine hydroxylation. Chem Biol. 2009;16(6):580–3.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Chinese Foundation for Hepatitis Prevention and Control Project (20120030) and the Medical research projects of Wuxi Hospital Management Center (ygzxl 1306).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Wuxi Higher Health Vocational Technology School, No. 305, Xinguang Road, Wuxi, 214028, China

    Li Li Lin, Li Wen Wang & Jing Chang

  2. Department of Pharmacy and Medical Appliances, Hangzhou Sanatorium of PLA, No. 27 Yang Gong Dike, Hangzhou, 310007, Zhejiang, China

    Wei Wang

  3. Cancer Research Institute, Hangzhou Cancer Hospital, No. 34 Yan Guan Road, Hangzhou, 310002, China

    ZhaoYang Hu

  4. Department of Orthopedics, Wuxi Third People’s Hospital Affiliated, School of Medicine, Nantong University, No. 585 Northern Xinyuan Rd, Wuxi, 214041, China

    HanGuang Qian

Authors
  1. Li Li Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. ZhaoYang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Wen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jing Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. HanGuang Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to HanGuang Qian.

Additional information

Li Li Lin and Wei Wang have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, L.L., Wang, W., Hu, Z. et al. Negative feedback of miR-29 family TET1 involves in hepatocellular cancer. Med Oncol 31, 291 (2014). https://doi.org/10.1007/s12032-014-0291-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0291-2

Keywords

Search

Navigation