TRIM66 promotes malignant progression of hepatocellular carcinoma by inhibiting E-cadherin expression through the EMT pathway
Authors: W-W Zhang
C-T Zeng
Y-W Pan
X-Q Zhao
B Liang
H-G Zhang
J Feng
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: TRIM66; hepatocellular carcinoma; regulatory role; development; mechanism
Affiliations: Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China. .

Abstract:  Objective: The aim of this study was to explore the regulatory role of TRIM66 in the development of hepatocellular carcinoma (HCC), and to investigate its underlying mechanism. Patients and methods: A total of 88 pairs of HCC tissues and para-cancerous tissues were surgically resected. The expression of TRIM66 was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between TRIM66 expression and clinic-pathologic characteristics of HCC patients was analyzed. Follow-up data of enrolled HCC patients were collected for survival analysis. Subsequently, TRIM66 expression in HCC cells was determined by qRT-PCR as well. By constructing si-TRIM66, the biological performances of transfected HCC cells were determined using cell counting kit-8 (CCK-8), colony formation and transwell assay. Western blot was performed to measure the protein expressions of relative genes in epithelial-mesenchymal transition (EMT) pathway. Finally, HCC cells were co-transfected with si-TRIM66 and pcDNA-E-cadherin, followed by detection of invasive and migratory abilities. Results: TRIM66 was highly expressed in HCC tissues compared with that of para-cancerous tissues. High expression of TRIM66 was positively correlated with tumor stage, lymph node metastasis and distant metastasis, whereas not correlated with age and sex of HCC patients. Kaplan-Meier curves revealed that a higher expression of TRIM66 was associated with worse prognosis of HCC. Similarly, TRIM66 was also highly expressed in HCC cells. The knockdown of TRIM66 in HCC cells significantly inhibited the proliferative, invasive and migratory abilities of transfected cells. However, TRIM66 down-regulation significantly induced cell apoptosis. Western blot results showed that TRIM66 knockdown in HCC cells markedly downregulated the protein expressions of E-cadherin, N-cadherin, Vimentin and β-catenin. The inhibited migration and invasion of HCC cells resulted from TRIM66 knockdown were partially reversed by E-cadherin overexpression. Conclusions: TRIM66 is highly expressed in HCC, which is positively correlated with tumor stage, lymph node metastasis and distant metastasis of HCC patients. In addition, TRIM66 promotes the malignant progression of HCC by inhibiting E-cadherin through the EMT pathway. 

Retracted: No

PubPeer comments:
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 2020 Editor s note. https: cancerres.aacrjournals.org content 80 2 364 The editors are publishing this note to alert readers to concerns about this article (1). There is evidence of inconsistent splicing in several Western blot images. Specifically, in Fig. 1C, splicing is evident between the first and second lanes of all proteins except p-JNK. Likewise, in Fig. 2A, there is splicing between the 10th and 11th lanes of Flag, which is not evident in p-MEK and MEK. Finally, there is inconsistent splicing throughout the Western blot image in Fig. 3A. Reference 1.u21b5Li SP, Junttila MR, Han J, Ku00e4hu00e4ri VM, Westermarck J. p38 Mitogen-activated protein kinase pathway suppresses cell survival by inducing dephosphorylation of mitogen-activated protein extracellular signal-regulated kinase kinase1,2. Cancer Res 2003;63:3473u20137. ,