Aberrant DNA Methylation, Expression, and Occurrence of Transcript Variants of the ABC Transporter ABCA7 in Breast Cancer

Sep 24, 2026

The ABC transporter ABCA7 is aberrantly expressed across multiple cancer types, including breast cancer. The study examined epigenetic and genetic alterations, as well as alternative splicing variants of ABCA7, and evaluated links to ABCA7 expression using patient tumor tissues. CpGs at the exon 5–intron 5 boundary were found aberrantly methylated in a molecular subtype-specific pattern, suggesting epigenetic field cancerization. In cell models, promoter/exon 1, intron 1, and exon 5–intron 5 methylation did not correlate with ABCA7 mRNA levels; qPCR detected intron-containing transcripts. Intron-containing transcripts were induced by doxorubicin or paclitaxel and associated with dysregulated splicing factors by shotgun proteomics.

LanguageEnglish

CategoryHealthcare

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Pages34

Reading Time1 h 26 min

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Abstract

Introduction

cells Article Aberrant DNA Methylation, Expression, and Occurrence of Transcript Variants of the ABC TransporterABCA7 in Breast Cancer Katja Zappe 1, Antonio Kopic 1, Alexandra Scheichel 1, Ann-Katrin Schier 1, Lukas Emanuel Schmidt 1, Yasmin Borutzki 1,2, Heidi Miedl 3, Martin Schreiber 3, Theresa Mendrina 2,4, Christine Pirker 4, Georg Pfeiler 5, Stefan Hacker 6, Werner Haslik 6, Dietmar Pils 7, Andrea Bileck 1,8, Christopher Gerner 1,8, Samuel Meier-Menches 1,2,8, Petra Heffeter 4 and Margit Cichna-Markl 1, * Citation: Zappe, K.; Kopic, A.; Scheichel, A.; Schier, A.-K.; Schmidt, L.E.; Borutzki, Y.; Miedl, H.; Schreiber, M.; Mendrina, T.; Pirker, C.; et al. Aberrant DNA Methylation, Expression, and Occurrence of Transcript Variants of the ABC Transporter ABCA7 in Breast Cancer. Cells 2023, 12, 1462. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cells12111462](10.3390/cells12111462) Academic Editors: Tiziana Triulzi and Marilena V. Iorio Received: 28 February 2023 Revised: 9 May 2023 Accepted: 16 May 2023 Published: 24 May 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria 2 Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria 3 Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria 4 Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria 5 Division of Gynecology and Gynecological Oncology, Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria 6 Department of Plastic and Reconstructive Surgery, Medical University of Vienna, 1090 Vienna, Austria 7 Division of Visceral Surgery, Department of General Surgery and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria 8 Joint Metabolome Facility, University of Vienna and Medical University of Vienna, 1090 Vienna, Austria * [Correspondence: margit.cichna@univie.ac.at](Correspondence: margit.cichna@univie.ac.at); Tel.: +43-(0)14277-52374 Abstract: The ABC transporter ABCA7 has been found to be aberrantly expressed in a variety of cancer types, including breast cancer. We searched for speciﬁc epigenetic and genetic alterations and alternative splicing variants of ABCA7 in breast cancer and investigated whether these alterations are associated with ABCA7 expression. By analyzing tumor tissues from breast cancer patients, we found CpGs at the exon 5–intron 5 boundary aberrantly methylated in a molecular subtype-speciﬁc manner. The detection of altered DNA methylation in tumor-adjacent tissues suggests epigenetic ﬁeld cancerization. In breast cancer cell lines, DNA methylation levels of CpGs in promoter-exon 1, intron 1, and at the exon 5–intron 5 boundary were not correlated with ABCA7 mRNA levels. By qPCR involving intron-speciﬁc and intron-ﬂanking primers, we identiﬁed intron-containing ABCA7 mRNA transcripts. The occurrence of intron-containing transcripts was neither molecular subtypespeciﬁc nor directly correlated with DNA methylation at the respective exon–intron boundaries. Treatment of breast cancer cell lines MCF-7, BT-474, SK-BR3, and MDA-MB-231 with doxorubicinor paclitaxel for 72 h resulted in altered ABCA7 intron levels. Shotgun proteomics revealed that an increase in intron-containing transcripts was associated with signiﬁcant dysregulation of splicing factors linked to alternative splicing. Keywords: ABCA7; ABC transporter; breast cancer; DNA methylation; gene expressi

FAQs

What epigenetic alteration was identified in ABCA7 in breast cancer tissues?

CpGs at the exon 5–intron 5 boundary were aberrantly methylated in a molecular subtype-specific manner.

Do DNA methylation levels at exon 1 or the exon 5–intron 5 boundary correlate with ABCA7 mRNA expression?

No. DNA methylation of CpGs in promoter-exon 1, intron 1, and at the exon 5–intron 5 boundary was not correlated with ABCA7 mRNA levels in breast cancer cell lines.

How were intron-containing ABCA7 transcripts detected and how do treatments affect them?

Intron-containing ABCA7 mRNA transcripts were identified by qPCR using intron-specific and intron-flanking primers. Treatment with doxorubicin or paclitaxel for 72 hours altered ABCA7 intron levels.

Sep 24, 2026

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