Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion

  • Authors:
    • Linlin Li
    • Lei Dong
    • Xiaotong Qu
    • Shi Jin
    • Xiupeng Lv
    • Guang Tan
  • View Affiliations

  • Published online on: February 17, 2016     https://doi.org/10.3892/ijo.2016.3398
  • Pages: 1639-1649
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has been demonstrated to have significant effects on tumor migration by previous studies, but its specific contribution to hepatocellular carcinoma (HCC) is currently unknown. The aim of this study was to evaluate the prognostic value of TRIM16 and investigate its functional roles in HCC. The expression of TRIM16 in HCC patient samples were examined using qRT-PCR and western blotting. HCC cell lines with either TRIM16 overexpression or knockdown were established. The effect of TRIM16 on HCC cell migration and invasion was investigated using these cells. Compared with paired normal liver tissues in clinical cancer samples, we found that the expression of TRIM16 was significantly downregulated in HCC lesions. We also found knockdown of TRIM16 promoted epithelial-mesenchymal transition (EMT) in a manner associated with HCC metastasis in vitro and in vivo. Mechanistically, TRIM16 inhibited ZEB2 expression, which in turn inhibited transcription of the pivotal ZEB2 target gene E-cadherin. RNA interference-mediated silencing of ZEB2 attenuated shTRIM16-enhanced cell migration and invasion. In conclusion, our findings define TRIM16 as an inhibitor of EMT and metastasis in HCC that predicts poor clinical outcomes.

References

1 

DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS and Jemal A: Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 64:252–271. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Hato T, Goyal L, Greten TF, Duda DG and Zhu AX: Immune checkpoint blockade in hepatocellular carcinoma: Current progress and future directions. Hepatology. 60:1776–1782. 2014. View Article : Google Scholar : PubMed/NCBI

4 

El-Serag HB and Kanwal F: Epidemiology of hepatocellular carcinoma in the United States: Where are we? Where do we go? Hepatology. 60:1767–1775. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Marshall GM, Bell JL, Koach J, Tan O, Kim P, Malyukova A, Thomas W, Sekyere EO, Liu T, Cunningham AM, et al: TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. Oncogene. 29:6172–6183. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Bell JL, Malyukova A, Holien JK, Koach J, Parker MW, Kavallaris M, Marshall GM and Cheung BB: TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other TRIM family members. PLoS One. 7:e374702012. View Article : Google Scholar : PubMed/NCBI

7 

Sutton SK, Koach J, Tan O, Liu B, Carter DR, Wilmott JS, Yosufi B, Haydu LE, Mann GJ, Thompson JF, et al: TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells. Oncotarget. 5:10127–10139. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Cheung BB, Koach J, Tan O, Kim P, Bell JL, D'andreti C, Sutton S, Malyukova A, Sekyere E, Norris M, et al: The retinoid signalling molecule, TRIM16, is repressed during squamous cell carcinoma skin carcinogenesis in vivo and reduces skin cancer cell migration in vitro. J Pathol. 226:451–462. 2012. View Article : Google Scholar :

9 

You H, Ding W and Rountree CB: Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-beta. Hepatology. 51:1635–1644. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Wang Y, Wen M, Kwon Y, Xu Y, Liu Y, Zhang P, He X, Wang Q, Huang Y, Jen KY, et al: CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression. Cancer Res. 74:520–531. 2014. View Article : Google Scholar :

11 

Wang Y, Zhang P, Liu Z, Wang Q, Wen M, Wang Y, Yuan H, Mao JH and Wei G: CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to erlotinib via transcriptional regulation of EGFR. Mol Cancer. 13:2522014. View Article : Google Scholar : PubMed/NCBI

12 

Sun Y, Wang Y, Fan C, Gao P, Wang X, Wei G and Wei J: Estrogen promotes stemness and invasiveness of ER-positive breast cancer cells through Gli1 activation. Mol Cancer. 13:1372014. View Article : Google Scholar : PubMed/NCBI

13 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Floor S, van Staveren WC, Larsimont D, Dumont JE and Maenhaut C: Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating-cancer stem cells: Distinct, overlapping or same populations. Oncogene. 30:4609–4621. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Hills CE and Squires PE: The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine Growth Factor Rev. 22:131–139. 2011.PubMed/NCBI

16 

Yilmaz M and Christofori G: EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 28:15–33. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Huo X, Li S, Shi T, Suo A, Ruan Z and Yao Y: Tripartite motif 16 inhibits epithelial-mesenchymal transition and metastasis by down-regulating sonic hedgehog pathway in non-small cell lung cancer cells. Biochem Biophys Res Commun. 460:1021–1028. 2015. View Article : Google Scholar : PubMed/NCBI

18 

van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, Machat G, Grubinger M, Huber H and Mikulits W: Epithelial-mesenchymal transition in hepatocellular carcinoma. Future Oncol. 5:1169–1179. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

April 2016
Volume 48 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Li, L., Dong, L., Qu, X., Jin, S., Lv, X., & Tan, G. (2016). Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion. International Journal of Oncology, 48, 1639-1649. https://doi.org/10.3892/ijo.2016.3398
MLA
Li, L., Dong, L., Qu, X., Jin, S., Lv, X., Tan, G."Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion". International Journal of Oncology 48.4 (2016): 1639-1649.
Chicago
Li, L., Dong, L., Qu, X., Jin, S., Lv, X., Tan, G."Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion". International Journal of Oncology 48, no. 4 (2016): 1639-1649. https://doi.org/10.3892/ijo.2016.3398