Display options
Share it on

Oncol Lett. 2017 Jun;13(6):4526-4532. doi: 10.3892/ol.2017.5971. Epub 2017 Apr 03.

TUC338 promotes cell migration and invasion by targeting TIMP1 in cervical cancer.

Oncology letters

Qin Li, Feiyang Shen, Chenghai Wang

Affiliations

  1. Department of Clinic, School of Medicine, Yangzhou Polytechnic College, Yangzhou, Jiangsu 225009, P.R. China.
  2. School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China.
  3. Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China.
  4. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
  5. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.

PMID: 28599453 PMCID: PMC5453013 DOI: 10.3892/ol.2017.5971

Abstract

Ultraconserved regions (UCRs) are non-protein-coding gene sequences that are strictly conserved across numerous distinct species. It has been demonstrated previously that UCRs encoding non-coding RNAs serve as regulators of gene expression. In recent decades, there has been increasing evidence for the involvement of UCRs in carcinogenesis. In previous studies, the non-coding RNA transcribed ultraconserved element 338 (TUC338) was identified to serve an oncogenic role in hepatocellular cancer; however, thus far, the role of TUC338 in cervical cancer (CC) remains undefined. The results of the present study revealed that TUC338 is significantly upregulated in CC tissues and cell lines, and that the upregulation of TUC338 is associated with lymph node metastasis. Transfection with small interfering RNA (siRNA) against TUC338 could markedly inhibit cell migration and invasion in HeLa and C33A CC cell lines. Using a dual-luciferase reporter assay, tissue inhibitor of metalloproteinase 1 (TIMP1) was demonstrated to be negatively regulated by TUC338 at the post-transcriptional level, via a specific target site within the 3' untranslated region. The expression of TIMP1 was also observed to be inversely associated with TUC338 expression in CC tissues. Overexpression of TIMP1 with MigRI-TIMP1-green fluorescent protein inhibited CC cell migration and invasion and downregulated matrix metalloproteinase 9, resembling the effects of TUC338 siRNA. Therefore, the results of the present study suggest that TUC338 acts as a novel oncogene by targeting the TIMP1 gene, and inhibiting CC cell migration and invasion.

Keywords: cervical cancer; invasion; matrix metalloproteinase 9; migration; tissue inhibitor of metalloproteinase 1; transcribed ultraconserved element 338

References

  1. Front Genet. 2011 Sep 05;2:58 - PubMed
  2. Oncol Lett. 2015 May;9(5):2218-2224 - PubMed
  3. Cancers (Basel). 2014 Jan 27;6(1):240-96 - PubMed
  4. Methods. 2001 Dec;25(4):402-8 - PubMed
  5. Science. 2007 Aug 17;317(5840):915 - PubMed
  6. Int J Clin Exp Pathol. 2013 Dec 15;7(1):246-54 - PubMed
  7. Science. 2008 Sep 26;321(5897):1785-7 - PubMed
  8. Oncogene. 2010 Jun 17;29(24):3583-92 - PubMed
  9. Nature. 2006 May 4;441(7089):87-90 - PubMed
  10. Otolaryngol Pol. 2016 Jun 30;70(3):32-43 - PubMed
  11. Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):786-91 - PubMed
  12. Cell. 2006 Nov 17;127(4):679-95 - PubMed
  13. Neoplasma. 2015 ;62(4):541-9 - PubMed
  14. J Neuropathol Exp Neurol. 2015 Apr;74(4):293-304 - PubMed
  15. Biochem Pharmacol. 2014 Sep 15;91(2):202-16 - PubMed
  16. Folia Histochem Cytobiol. 2012 Apr 24;50(1):12-9 - PubMed
  17. Carcinogenesis. 2009 Mar;30(3):544-5; author reply 546 - PubMed
  18. Cancer Cell. 2007 Sep;12(3):215-29 - PubMed
  19. Oncogene. 2010 Dec 2;29(48):6390-401 - PubMed
  20. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90 - PubMed
  21. Pol J Pathol. 2014 Dec;65(4):296-304 - PubMed
  22. J Biol Chem. 1999 May 7;274(19):13066-76 - PubMed
  23. PLoS One. 2014 Apr 11;9(4):e94370 - PubMed
  24. Rev Obstet Gynecol. 2010 Winter;3(1):33-4 - PubMed
  25. Int J Cancer. 2000 Aug 1;87(3):336-42 - PubMed

Publication Types