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A novel long non‑coding RNA regulates the integrin, ITGA2 in breast cancer

Citation

Verhoeff, TJ and Holloway, AF and Dickinson, JL, A novel long non‑coding RNA regulates the integrin, ITGA2 in breast cancer, Breast Cancer Research and Treatment, 192 pp. 89-100. ISSN 0167-6806 (2022) [Refereed Article]

Copyright Statement

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021

DOI: doi:10.1007/s10549-021-06496-x

Abstract

Purpose

ITGA2 encodes the integrin, α2 which mediates metastatic progression, and is a predictor of poor prognosis and chemoresistance in breast cancer. Decreased ITGA2 promoter methylation is implicated as a driver of increased gene expression in aggressive prostate and pancreatic tumours, however the contribution of altered methylation to ITGA2 expression changes in breast tumours has not been examined.

Methods

ITGA2 gene methylation and gene expression was examined in publicly available breast cancer datasets, and ITGA2 promoter methylation was mapped by targeted bisulphite sequencing analysis in breast tumour cell lines. The expression of a putative regulatory long noncoding RNA (lncRNA) was examined by qPCR and itsí functionality was investigated using gene knockdown (antisense oligonucleotides) and over expression in breast cancer cell lines.

Results

In breast tumours and breast cancer cell lines the ITGA2 promoter is largely unmethylated, with gene expression variable in tumour subtypes, irrespective of promoter methylation. A novel lncRNA (AC025180.1;ENSG00000249899), named herein I2ALR, was identified at the ITGA2 gene locus, and was variably expressed in breast tumours and breast cancer cell subtypes. I2LAR knockdown resulted in upregulation of ITGA2 gene expression, whilst over-expression of I2ALR resulted in downregulation of ITGA2 mRNA. Further, examination of two downstream targets of ITGA2 associated with breast tumor stemness and metastasis (CCND1 and ACLY), revealed concomitant gene expression changes in response to I2ALR modulation.

Conclusion

I2ALR represents a novel regulatory molecule targeting ITGA2 expression in breast tumours; a finding of significant and topical interest to the development of therapeutics targeting this integrin.

Item Details

Item Type:Refereed Article
Keywords:lncRNA, gene regulation, metastasis, integrins, ITGA2, epigenetic
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Cancer cell biology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Verhoeff, TJ (Mr Tristan Verhoeff)
UTAS Author:Holloway, AF (Professor Adele Holloway)
UTAS Author:Dickinson, JL (Professor Joanne Dickinson)
ID Code:148984
Year Published:2022
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-02-26
Last Modified:2022-03-10
Downloads:0

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