J Cancer 2020; 11(6):1412-1423. doi:10.7150/jca.31903 This issue Cite

Research Paper

Downregulation of EVI1 Expression Inhibits Cell Proliferation and Induces Apoptosis in Hilar Cholangiocarcinoma via the PTEN/AKT Signalling Pathway

Xiao-ming Zhang1,2, Zeng-li Liu1, Bo Qiu3, Yun-fei XU1, Chang Pan4✉, Zong-li Zhang1✉

1. Department of general surgery, Qilu Hospital of Shandong University, No. 107, Wenhua Xi Road, Jinan, 250012, China.
2. Department of general surgery, Linyi People's Hospital, Linyi, 276000, China.
3. Department of general surgery, Qilu Hospital of Shandong University (Qingdao), 266035, China.
4. Department of emergency, Qilu Hospital of Shandong University, No. 107, Wenhua Xi Road, Jinan, 250012, China.

Citation:
Zhang Xm, Liu Zl, Qiu B, XU Yf, Pan C, Zhang Zl. Downregulation of EVI1 Expression Inhibits Cell Proliferation and Induces Apoptosis in Hilar Cholangiocarcinoma via the PTEN/AKT Signalling Pathway. J Cancer 2020; 11(6):1412-1423. doi:10.7150/jca.31903. https://www.jcancer.org/v11p1412.htm
Other styles

File import instruction

Abstract

Aims: Hilar cholangiocarcinoma (HCCA) is a tumour with high malignancy, low surgical resection potential, and a poor prognosis. Ecotropic Viral Integration site 1 (EVI1) is a transcriptional regulator that has been proven to be associated with tumourigenesis and progression in many human solid tumours. However, the expression of EVI1 and its role in HCCA progression remain unclear. The aim of this study was to clarify the association between EVI1 expression and clinical outcomes in patients with HCCA.

Methods: The expression of EVI1 in HCCA tissue samples and cell lines was examined by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC). Kaplan-Meier analysis was used for survival analysis. A log-rank test was performed for univariate analysis of survival, and a Cox regression model was utilized for multivariate analysis of survival. Cell proliferation was measured by cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. The cell cycle was evaluated by flow cytometry. Cell apoptosis was detected by flow cytometry and a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) assay. In vivo tumour growth was observed for xenografts in nude mice.

Results: EVI1 expression was upregulated in HCCA tissue samples and correlated with a poor prognosis. In clinical specimens, the expression of EVI1 correlated with tumour histological grade and tumour size. Knocking down EVI1 expression reduced HCCA cell proliferation, blocked cell cycle progression, and promoted apoptosis in vitro and in vivo. Furthermore, we found that EVI1 could regulate the AKT signalling pathway by regulating PTEN levels in HCCA.

Conclusion: Our data revealed that EVI1 played important roles in HCCA tumourigenesis and development. Our findings suggest that EVI1 may be a potentially useful therapeutic target in HCCA.

Keywords: Hilar cholangiocarcinoma, EVI1, Cell proliferation, PTEN


Citation styles

APA
Zhang, X.m., Liu, Z.l., Qiu, B., XU, Y.f., Pan, C., Zhang, Z.l. (2020). Downregulation of EVI1 Expression Inhibits Cell Proliferation and Induces Apoptosis in Hilar Cholangiocarcinoma via the PTEN/AKT Signalling Pathway. Journal of Cancer, 11(6), 1412-1423. https://doi.org/10.7150/jca.31903.

ACS
Zhang, X.m.; Liu, Z.l.; Qiu, B.; XU, Y.f.; Pan, C.; Zhang, Z.l. Downregulation of EVI1 Expression Inhibits Cell Proliferation and Induces Apoptosis in Hilar Cholangiocarcinoma via the PTEN/AKT Signalling Pathway. J. Cancer 2020, 11 (6), 1412-1423. DOI: 10.7150/jca.31903.

NLM
Zhang Xm, Liu Zl, Qiu B, XU Yf, Pan C, Zhang Zl. Downregulation of EVI1 Expression Inhibits Cell Proliferation and Induces Apoptosis in Hilar Cholangiocarcinoma via the PTEN/AKT Signalling Pathway. J Cancer 2020; 11(6):1412-1423. doi:10.7150/jca.31903. https://www.jcancer.org/v11p1412.htm

CSE
Zhang Xm, Liu Zl, Qiu B, XU Yf, Pan C, Zhang Zl. 2020. Downregulation of EVI1 Expression Inhibits Cell Proliferation and Induces Apoptosis in Hilar Cholangiocarcinoma via the PTEN/AKT Signalling Pathway. J Cancer. 11(6):1412-1423.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image