Tumor Biology

, Volume 35, Issue 12, pp 11829–11835 | Cite as

Nucleotidyl transferase TUT1 inhibits lipogenesis in osteosarcoma cells through regulation of microRNA-24 and microRNA-29a

  • De-qiu Zhu
  • Yue-fen Lou
  • Zhi-gao He
  • Min Ji
Research Article


Osteosarcoma is the most common type of bone cancer. In the present study, by way of PCR-based microarrays, we found that TUT1, a nucleotidyl transferase, was significantly downregulated in osteosarcoma, compared with adjacent normal tissues. In the current study, we performed PCR-based microarrays using the cDNA prepared from osteosarcoma and adjacent normal tissues. The enforced expression of TUT1 was able to inhibit cell proliferation in U2OS and MG63 cells, while its knockdown using small interfering RNA (siRNA) oligos promoted cell proliferation. At the molecular level, we found that TUT1 could inhibit the expression levels of PPARgamma and SREBP-1c, two key regulators in lipogenesis, through upregulation of microRNA-24 and microRNA-29a. Therefore, our results suggest that TUT1 may act as a tumor suppressor for osteosarcoma, which might provide a novel mechanism for the tumor development.


Osteosarcoma cells MicroRNA-24 TUT1 MicroRNA-29a 


Conflicts of interest


Supplementary material

13277_2014_2395_MOESM1_ESM.doc (231 kb)
Supplementary Fig. 1 (DOC 231 kb)
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Supplementary Fig. 2 (DOC 218 kb)
13277_2014_2395_MOESM3_ESM.doc (110 kb)
Supplementary Fig. 3 (DOC 110 kb)
13277_2014_2395_MOESM4_ESM.doc (124 kb)
Supplementary Fig. 4 (DOC 123 kb)


  1. 1.
    Luetke A, Meyers PA, Lewis I, Juergens H. Osteosarcoma treatment—where do we stand? A state of the art review. Cancer Treat Rev. 2014;40:523–32.PubMedCrossRefGoogle Scholar
  2. 2.
    Botter SM, Neri D, Fuchs B. Recent advances in osteosarcoma. Curr Opin Pharmacol. 2014;16C:15–23.CrossRefGoogle Scholar
  3. 3.
    Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14:535–48.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14:475–88.PubMedCrossRefGoogle Scholar
  5. 5.
    Tessitore A, Cicciarelli G, Del VF, Gaggiano A, Verzella D, Fischietti M, et al. MicroRNAs in the DNA damage/repair network and cancer. Int J Genomics. 2014;2014:820248.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Miao J, Wu S, Peng Z, Tania M, Zhang C. MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects. Tumour Biol. 2013;34:2093–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25:398–406.PubMedCrossRefGoogle Scholar
  8. 8.
    Zhou G, Shi X, Zhang J, Wu S, Zhao J. MicroRNAs in osteosarcoma: from biological players to clinical contributors, a review. J Int Med Res. 2013;41:1–12.PubMedCrossRefGoogle Scholar
  9. 9.
    Song QC, Shi ZB, Zhang YT, Ji L, Wang KZ, Duan DP, et al. Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients. Oncol Rep. 2014;31:1263–70.PubMedGoogle Scholar
  10. 10.
    Cai H, Lin L, Cai H, Tang M, Wang Z. Combined microRNA-340 and ROCK1 mRNA profiling predicts tumor progression and prognosis in pediatric osteosarcoma. Int J Mol Sci. 2014;15:560–73.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Knouf EC, Wyman SK, Tewari M. The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance. PLoS One. 2013;8:e69630.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Dweep H, Sticht C, Gretz N. In-silico algorithms for the screening of possible microRNA binding sites and their interactions. Curr Genomics. 2013;14:127–36.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Israel M, Schwartz L. The metabolic advantage of tumor cells. Mol Cancer. 2011;10:70.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Rochefort H, Chalbos D. The role of sex steroid receptors on lipogenesis in breast and prostate carcinogenesis: a viewpoint. Horm Cancer. 2010;1:63–70.PubMedCrossRefGoogle Scholar
  15. 15.
    Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV, Smans K. Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res. 2013;52:585–9.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, et al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013;51:506–18.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Jeon SM, Chandel NS, Hay N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature. 2012;485:661–5.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Li J, Dong L, Wei D, Wang X, Zhang S, Li H. Fatty acid synthase mediates the epithelial-mesenchymal transition of breast cancer cells. Int J Biol Sci. 2014;10:171–80.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Mao JH, Zhou RP, Peng AF, Liu ZL, Huang SH, Long XH, et al. MicroRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN. Oncol Lett. 2012;4:1125–9.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Long XH, Mao JH, Peng AF, Zhou Y, Huang SH, Liu ZL. Tumor suppressive microRNA-424 inhibits osteosarcoma cell migration and invasion via targeting fatty acid synthase. Exp Ther Med. 2013;5:1048–52.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Cheng C, Chen ZQ, Shi XT. MicroRNA-320 inhibits osteosarcoma cells proliferation by directly targeting fatty acid synthase. Tumour Biol. 2014 Jan 5.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Pharmacy, Shanghai Tongji HospitalShanghaiChina
  2. 2.Department of PharmacyThe Branch of the First People’s Hospital of Shanghai City (the fourth hospital)ShanghaiChina
  3. 3.Department of PharmacyEast Hospital, Tongji University School of MedicineShanghaiChina
  4. 4.Department of PharmacyYangpu Hospital, Tongji University School of MedicineShanghaiChina

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