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Breast Cancer Research
Published in: Breast Cancer Research 1/2022

Open Access 01-12-2022 | Breast Cancer | Research

Progesterone modulates the DSCAM-AS1/miR-130a/ESR1 axis to suppress cell invasion and migration in breast cancer

Authors: Neelima Yadav, Roma Sunder, Sanket Desai, Bhasker Dharavath, Pratik Chandrani, Mukul Godbole, Amit Dutt

Published in: Breast Cancer Research | Issue 1/2022

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Abstract

Background

A preoperative-progesterone intervention increases disease-free survival in patients with breast cancer, with an unknown underlying mechanism. We elucidated the role of non-coding RNAs in response to progesterone in human breast cancer.

Methods

Whole transcriptome sequencing dataset of 30 breast primary tumors (10 tumors exposed to hydroxyprogesterone and 20 tumors as control) were re-analyzed to identify differentially expressed non-coding RNAs followed by real-time PCR analyses to validate the expression of candidates. Functional analyses were performed by genetic knockdown, biochemical, and cell-based assays.

Results

We identified a significant downregulation in the expression of a long non-coding RNA, Down syndrome cell adhesion molecule antisense DSCAM-AS1, in response to progesterone treatment in breast cancer. The progesterone-induced expression of DSCAM-AS1 could be effectively blocked by the knockdown of progesterone receptor (PR) or treatment of cells with mifepristone (PR-antagonist). We further show that knockdown of DSCAM-AS1 mimics the effect of progesterone in impeding cell migration and invasion in PR-positive breast cancer cells, while its overexpression shows an opposite effect. Additionally, DSCAM-AS1 sponges the activity of miR-130a that regulates the expression of ESR1 by binding to its 3’-UTR to mediate the effect of progesterone in breast cancer cells. Consistent with our findings, TCGA analysis suggests that high levels of miR-130a correlate with a tendency toward better overall survival in patients with breast cancer.

Conclusion

This study presents a mechanism involving the DSCAM-AS1/miR-130a/ESR1 genomic axis through which progesterone impedes breast cancer cell invasion and migration. The findings highlight the utility of progesterone treatment in impeding metastasis and improving survival outcomes in patients with breast cancer.
Appendix
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Metadata
Title
Progesterone modulates the DSCAM-AS1/miR-130a/ESR1 axis to suppress cell invasion and migration in breast cancer
Authors
Neelima Yadav
Roma Sunder
Sanket Desai
Bhasker Dharavath
Pratik Chandrani
Mukul Godbole
Amit Dutt
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2022
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-022-01597-x

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