TY - JOUR
T1 - Aberrant DNA Methylation, Expression, and Occurrence of Transcript Variants of the ABC Transporter ABCA7 in Breast Cancer
AU - Zappe, Katja
AU - Kopic, Antonio
AU - Scheichel, Alexandra
AU - Schier, Ann Katrin
AU - Schmidt, Lukas Emanuel
AU - Borutzki, Yasmin
AU - Miedl, Heidi
AU - Schreiber, Martin
AU - Mendrina, Theresa
AU - Pirker, Christine
AU - Pfeiler, Georg
AU - Hacker, Stefan
AU - Haslik, Werner
AU - Pils, Dietmar
AU - Bileck, Andrea
AU - Gerner, Christopher
AU - Meier-Menches, Samuel
AU - Heffeter, Petra
AU - Cichna-Markl, Margit
N1 - Accession Number: WOS:001006431300001
PubMed ID: 37296582
PY - 2023/6
Y1 - 2023/6
N2 - 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 subtype-specific 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 doxorubicin or 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.
AB - 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 subtype-specific 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 doxorubicin or 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.
KW - ABC transporter
KW - ABCA7
KW - alternative splicing
KW - breast cancer
KW - DNA methylation
KW - doxorubicin
KW - gene expression
KW - intron retention/altered intron termination
KW - mass spectrometry-based shotgun proteomics
KW - paclitaxel
UR - http://www.scopus.com/inward/record.url?scp=85161262638&partnerID=8YFLogxK
U2 - 10.3390/cells12111462
DO - 10.3390/cells12111462
M3 - Article
C2 - 37296582
AN - SCOPUS:85161262638
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 11
M1 - 1462
ER -