Page 133 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

SDIRSACR Oncology Insights

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Investigation of hsa_circ_0044969 mediated regulation of PPM1D gene expression in breast cancer

Sibel Karaman , Merve Demirbag Karaali , Serap Celikler , Elif Uz Yildirim 4
2
1
3
1Department of Molecular Biology and Genetics, Graduate School of Natural and Applied Sciences,
Bursa Uludağ University, Bursa, Turkey
2Department of Biology, Graduate School of Natural and Applied Sciences, Bursa Uludağ University,Bursa, Turkey
3Department of Biology, Faculty of Arts and Sciences, Bursa Uludağ University, Bursa, Turkey
4Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Bursa Uludağ
University, Bursa, Turkey

Keywords: PPM1D, circRNA, breast cancer, post-transcriptional gene regulation

Background: Breast cancer is one of the most common types of cancer. It has been published that its pathology
has been associated with the dysregulation of numerous genes, environmental factors and various epigenetic
mechanisms. Among the epigenetic factors, noncoding RNAs have emerged as important players in breast cancer
pathology. The importance of circular RNAs, covalently closed noncoding RNAs, has increasead in recent years, since it
has been understood that one of their functions is to sponge miRNAs and prevent them from binding to target mRNAs.
PPM1D (protein phosphatase, Mg2+/Mn2+ dependent 1D) is one of the negative regulators of the cell stress response
and was associated with aggressive tumors.
Materials and Methods: In this study, we aimed to investigate the expression profile of hsa_circ_0044969 and explore
its potential role as a regulator of PPM1D through circRNA-miRNA-mRNA axis in breast cancer. MCF7 and MDA-MB-231
breast cancer cell lines, along with the normal breast epithelial cell line MCF10A, were used as study samples and the
expression levels of has_circ_00449696 and PPM1D were measured by qRT-PCR.
Results: Both PPM1D mRNA and hsa_circ_00449696 are upregulated in breast cancer cell lines compared to normal
breast epithelial. The expression profile of hsa_mir_1299 revealed downregulation only in MCF7 cells compared to
normal.
Conclusions: Our results show that the expression levels of both hsa_circ_0044969 and PPM1D increase in a parallel way
in breast cancer. Further investigation is required to elucidate the molecular mechanisms underlying this correlation,
particularly within the circRNA-miRNA-mRNA regulatory axis.

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HRD testing doubled the number of ovarian cancer patients eligible for PARP inhibitor therapy

Katarina Živić, Milica Nedeljković, Radmila Janković, Miljana Tanić

Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, 11000 Belgrade, Serbia

Keywords: BRCA1, BRCA2, Ovarian Cancer, NGS, HRD, Olaparib

Background: Ovarian cancer remains one of the most lethal gynaecological cancers, with very few symptoms and a five-
year survival rate of about 40%. Treatment options are scarce, consisting of surgery and platinum-based chemotherapy
in the first-line setting, with potential PARP inhibitor use for patients with mutations in BRCA1/2 genes. In patients
with ovarian cancer, since 2025 in Serbia, the deficiency of the homologous recombination repair pathway (HRD) is a
predictive biomarker for the use of PARP inhibitors in newly diagnosed patients.
Materials and methods: The starting material was FFPE tissue from ovarian cancer patients sent for HRD testing
from all health centers in Serbia. The total number of HRD tested patients was 203, and testing was performed in
the Laboratory for Molecular Genetics at IORS or in the private molecular diagnostic laboratory – Genotypos Science
Labs in Greece. For evaluating HRD status, we used the SophiaDDM Dx HRD solution kit that covers 28 HRR genes
and evaluates the genomic instability signature (GIS) by lpWGS. GIS>0 and/or mutations in BRCA1/2 were considered
HRD-positive samples. In the Genotypos laboratory, the AmoyDx HRD Focus Panel was used, which covers BRCA1/2
genes, and the cut-off for GSS was 50. Testing was performed by NGS using the NextSeq500 system (Illumina). Pair-end
reading was used, and a cut-off of 5% for the variant allele frequency was applied with minimum coverage of 400x. The

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