ArticleCellular and molecular life sciences : CMLS2024
CENPA knockdown restrains cell progression and tumor growth in breast cancer by reducing PLA2R1 promoter methylation and modulating PLA2R1/HHEX axis.
Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- CENP-A in cancer: from centromere identity to genome instability.Molecular biology reports · 2026Review
- Centromere Protein I, a Cell Cycle Checkpoint Gene, Accelerates Tumor Progression via the Hippo Pathway and Mediates Immune Escape in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2025Article
- Integrated analysis of uterine leiomyosarcoma and leiomyoma utilizing TCGA and GEO data: a WGCNA and machine learning approach.Translational cancer research · 2025Article
- Article
- Advancing breast cancer biomarkers: a centromere-related gene signature integrated with single-cell analysis for prognostic prediction.Frontiers in immunology · 2025Article
- Exploration of the biological mechanisms of CENPA as an oncogene in glioma: Screening based on cancer functional status.Journal of cellular and molecular medicine · 2024Article
- Roles of Histone H2B, H3 and H4 Variants in Cancer Development and Prognosis.International journal of molecular sciences · 2024Review
- Investigation of differentially expressed genes related to cellular senescence between high-risk and non-high-risk groups in neuroblastoma.Frontiers in cell and developmental biology · 2024Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBreast cancer is a lethal malignancy affecting females worldwide. It has been reported that upregulated centromere protein A (CENPA) expression might indicate unfortunate prognosis and can function as a prognostic biomarker in breast cancer. This study aimed to investigate the accurate roles and downstream mechanisms of CENPA in breast cancer progression.
methodsCENPA protein levels in breast cancer tissues and cell lines were analyzed by Western blot and immunohistochemistry assays. We used gain/loss-of-function experiments to determine the potential effects of CENPA and phospholipase A2 receptor (PLA2R1) on breast cancer cell proliferation, migration, and apoptosis. Co-IP assay was employed to validate the possible interaction between CENPA and DNA methyltransferase 1 (DNMT1), as well as PLA2R1 and hematopoietically expressed homeobox (HHEX). PLA2R1 promoter methylation was determined using methylation-specific PCR assay. The biological capabilities of CENPA/PLA2R1/HHEX axis in breast cancer cells was determined by rescue experiments. In addition, CENPA-silenced MCF-7 cells were injected into mice, followed by measurement of tumor growth.
resultsCENPA level was prominently elevated in breast cancer tissues and cell lines. Interestingly, CENPA knockdown and PLA2R1 overexpression both restrained breast cancer cell proliferation and migration, and enhanced apoptosis. On the contrary, CENPA overexpression displayed the opposite results. Moreover, CENPA reduced PLA2R1 expression through promoting DNMT1-mediated PLA2R1 promoter methylation. PLA2R1 overexpression could effectively abrogate CENPA overexpression-mediated augment of breast cancer cell progression. Furthermore, PLA2R1 interacted with HHEX and promoted HHEX expression. PLA2R1 knockdown increased the rate of breast cancer cell proliferation and migration but restrained apoptosis, which was abrogated by HHEX overexpression. In addition, CENPA silencing suppressed tumor growth in vivo.
conclusionCENPA knockdown restrained breast cancer cell proliferation and migration and attenuated tumor growth in vivo through reducing PLA2R1 promoter methylation and increasing PLA2R1 and HHEX expression. We may provide a promising prognostic biomarker and novel therapeutic target for breast cancer.
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