Knockdown of TRIM15 inhibits the proliferation, migration and invasion of esophageal squamous cell carcinoma cells through inactivation of the Wnt/β-catenin signaling pathway


TRIM15 is a member of tripartite motif-containing protein (TRIM) protein family, which plays important roles in several cancers. The aim of the present study was to evaluate the role of TRIM15 in esophageal squamous cell carcinoma (ESCC). Our results showed that TRIM15 was upregulated in human ESCC tissues and cell lines. In vitro studies showed that knockdown of TRIM15 significantly inhibited the proliferation, migration, and invasion of ESCC cells. Knockdown of TRIM15 caused a significant increase in E-cadherin expression, as well as decreases in expression of N-cadherin and Vimentin proteins. Moreover, in vivo assay proved that tumor growth was suppressed by knockdown of TRIM15. Furthermore, the protein expression levels of β-catenin, C-myc, and CyclinD1 were markedly decreased in sh-TRIM15-infected ESCC cells. Additionally, treatment with LiCl reversed the inhibitory effects of TRIM15 knockdown on ESCC cells. In conclusion, these findings indicated that knockdown of TRIM15 blocked the growth and metastasis of ESCC in part through inhibiting the Wnt/β-catenin signaling pathway. Thus, TRIM15 might serve as a promising therapeutic target for ESCC.

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This study was supported by a standardized endoscopic diagnosis and treatment of early upper gastrointestinal cancer and related proteins (No.2018ZDXM-SF-055).

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Baicang Zou designed this manuscript. Li Zhang wrote this manuscript. Bin Qin, Shenhao Wang and Xiaojing Quan performed experiments. Jinhai Wang analyzed the data. Hongli Zhao revised the language of the manuscript; all the authors approved the manuscript for submission.

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Correspondence to Baicang Zou.

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Supplementary Information

Supplementary Fig. 1.

Immunohistochemistry staining of TRIM15 in human ESCC tissues and in adjacent non-tumor tissues. (PNG 40 kb)

Supplementary Fig. 3.

Sh2-TRIM15 suppresses the migration and invasion of ESCC cells. After 48 h post infection, transwell assay was used to assess cell migration and invasion. (A-B) Cell migration of EC-1 and KYSE-410 cells was measured. (C-D) Cell invasion of EC-1 and KYSE-410 cells was detected. n = 5. *p < 0.05 vs. sh-scramble group. (PNG 42 kb)

Supplementary Fig. 6.

The effects of TRIM15 overexpression on cell proliferation, migration and invasion in HET-1A esophageal epithelial cells. HET-1A cells were transfected with pcDNA3.1-TRIM15 or pcDNA3.1. (A) Cell proliferation was evaluated using CCK-8 assay. (B and C) Transwell assay was used to assess cell migration and invasion. *p < 0.05 vs. pcDNA3.1 group. (PNG 34 kb)

High Resolution Image (TIF 585 kb)

Supplementary Fig. 2.

Sh2-TRIM15 inhibits the proliferation of ESCC cells. EC-1 and KYSE-410 cells were infected with sh2-TRIM15 or sh-scramble. After 48 h post infection, the efficiency of TRIM15 knockdown was assessed by western blotting. (A-B) The protein expression levels of TRIM15 were decreased after infection with LV-sh2-TRIM15. (C-D) Cell proliferation of EC-1 and KYSE-410 cells was evaluated using CCK-8 assay. n = 6. *p < 0.05 vs. sh-scramble group. (PNG 772 kb)

High Resolution Image (TIF 2050 kb)

Supplementary Fig. 4.

Sh2-TRIM15 inhibits the EMT process in ESCC cells. The expression levels of three important EMT correlative markers including E-cadherin, N-cadherin and Vimentin in both TRIM15-silencing EC-1 (A) and KYSE-410 cells (B) were measured by using western blotting. n = 4. *p < 0.05 vs. sh-scramble group. (PNG 835 kb)

Supplementary Fig. 5.

Sh2-TRIM15 inhibits the Wnt/β-catenin pathway in ESCC cells. (A) The expression levels of β-catenin, C-myc, and CyclinD1 were measured by western blotting in TRIM15-silencinged EC-1 cells. (B-D) Quantification analysis of β-catenin, C-myc, and CyclinD1. n = 5. *p < 0.05 vs. sh-scramble group. (PNG 674 kb)

High Resolution Image (TIF 1775 kb)

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Zhang, L., Qin, B., Zou, B. et al. Knockdown of TRIM15 inhibits the proliferation, migration and invasion of esophageal squamous cell carcinoma cells through inactivation of the Wnt/β-catenin signaling pathway. J Bioenerg Biomembr (2021).

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  • Esophageal squamous cell carcinoma (ESCC)
  • TRIM15
  • Epithelial‐mesenchymal transition (EMT)
  • Metastasis
  • Wnt/β-catenin pathway