EPLIN, a putative tumour suppressor in colorectal cancer, implications in drug resistance

Zeng, Jianyuan, Sanders, Andrew J. ORCID: https://orcid.org/0000-0002-7997-5286, Lin, Ye, Hargest, Rachel ORCID: https://orcid.org/0000-0001-9830-3832, Ruge, Fiona and Jiang, Wen G. ORCID: https://orcid.org/0000-0002-3283-1111 2022. EPLIN, a putative tumour suppressor in colorectal cancer, implications in drug resistance. International Journal of Molecular Sciences 23 (23) , 15232. 10.3390/ijms232315232

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Abstract

Colorectal cancer is a serious threat to human health. Poor prognosis and frequently reported drug resistance urges research into novel biomarkers and mechanisms to aid in the understanding of the development and progression of colorectal cancer and to optimise therapeutic strategies. In the current study, we investigated the roles of a putative tumour suppressor, EPLIN, in colorectal cancer. Our clinical colorectal cancer cohort and online databases revealed a downregulation of EPLIN in colorectal cancer tissues compared with normal tissues. The reduced expression of EPLIN was associated with poor clinical outcomes of patients. In vitro cellular function assays showed that EPLIN elicited an inhibitory effect on cellular growth, adhesion, migration and invasion. Utilising a protein microarray on protein samples from normal and tumour patient tissues suggested HSP60, Her2 and other signalling events were novel potential interacting partners of EPLIN. It was further revealed that EPLIN and HSP60 were negative regulators of Her2 in colorectal cancer cells. The clinical cohort also demonstrated that expression of HSP60 and Her2 affected clinical outcomes, but most interestingly the combination of EPLIN, HSP60 and Her2 was able to identify patients with the most unfavourable clinical outcome by independently predicting patient overall survival and disease free survival. Furthermore, EPLIN and HSP60 exhibited potential to regulate cellular response to chemotherapeutic and EGFR/Her2 targeted therapeutic agents. In conclusion, EPLIN is an important prognostic factor for patients with colon cancer and reduced EPLIN in CRC contributes to aggressive traits of CRC cells and their responses to chemotherapeutic drugs. Collectively, EPLIN is a pivotal factor for the development and progression of colorectal cancer and has important clinical and therapeutic values in this cancer type.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	MDPI
ISSN:	1661-6596
Funders:	RealCan Fellowship (AJS) and Cardiff China Medical Scholarship (JZ)
Date of First Compliant Deposit:	1 December 2022
Date of Acceptance:	30 November 2022
Last Modified:	01 Mar 2024 17:59
URI:	https://orca.cardiff.ac.uk/id/eprint/154568

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