Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion Retraction in /10.3892/ijo.2023.5473

Li,Linlin; Dong,Lei; Qu,Xiaotong; Jin,Shi; Lv,Xiupeng; Tan,Guang

doi:10.3892/ijo.2016.3398

Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion

Retraction in: /10.3892/ijo.2023.5473

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

Affiliations: The 4th Medical Department of Liaoning Cancer Hospital and Institute, Dadong District, Shenyang, Liaoning 110042, P.R. China, Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, Shahekou District, Dalian, Liaoning 116001, P.R. China, Department of Second Neurology, The First Affiliated Hospital of Dalian Medical University, Xigang District, Dalian, Liaoning 116000, P.R. China, Department of Radiation Oncology, First Affiliated Hospital of Dalian Medical University, Shahekou District, Dalian, Liaoning 116001, P.R. China, Department of Hepatology, First Affiliated Hospital of Dalian Medical University, Shahekou District, Dalian, Liaoning 116001, P.R. China
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: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View 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