{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:02:33Z","timestamp":1785402153853,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"crossref","award":["UP A1H211"],"award-info":[{"award-number":["UP A1H211"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"crossref","award":["A1F812"],"award-info":[{"award-number":["A1F812"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"award":["UP A1H211"],"award-info":[{"award-number":["UP A1H211"]}],"id":[{"id":"https:\/\/ror.org\/05q60vz69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["A1F812"],"award-info":[{"award-number":["A1F812"]}],"id":[{"id":"https:\/\/ror.org\/05q60vz69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["NRF N1G655"],"award-info":[{"award-number":["NRF N1G655"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NRF N1G655"],"award-info":[{"award-number":["NRF N1G655"]}],"id":[{"id":"https:\/\/ror.org\/05s0g1g46","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001343","name":"University of Pretoria","doi-asserted-by":"crossref","award":["SAMRC A1H347"],"award-info":[{"award-number":["SAMRC A1H347"]}],"id":[{"id":"10.13039\/501100001343","id-type":"DOI","asserted-by":"crossref"}]},{"award":["SAMRC A1H347"],"award-info":[{"award-number":["SAMRC A1H347"]}],"id":[{"id":"https:\/\/ror.org\/00g0p6g84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epigenomes"],"abstract":"<jats:p>Background: Triple-negative breast cancer (TNBC) remains a clinical challenge due to its aggressive nature and the frequent emergence of therapeutic resistance. While the role of protein-coding genes in DNA repair is well-documented, the regulatory contributions of the non-coding genome, specifically long intergenic non-coding RNAs (lincRNAs), remain largely undefined. Objectives: In this study, we characterize the biological significance of LincRNA-BC7, a novel transcript identified within the breast cancer field effect. Methods: Through a combined in silico and in vitro approach, we investigated the transcriptional dynamics of the LincRNA-BC7\/miR-663a\/BRCA1 axis in response to the PARP inhibitor, Olaparib. Results: Our results demonstrate that Olaparib induces selective cytotoxicity in BRCA1-deficient MDA-MB-231 cells while sparing non-cancerous HEK293 cells, a response accompanied by a significant downregulation of LincRNA-BC7 and a reciprocal upregulation of BRCA1. Bioinformatics analysis through BLASTN, miRBase, and KEGG revealed that LincRNA-BC7 contains highly complementary binding sites for miR-663a, suggesting it functions as a competing endogenous RNA (ceRNA) or \u201cmolecular sponge.\u201d Conclusions: By sequestering miR-663a, LincRNA-BC7 appears to modulate the expression of critical signaling nodes within the PI3K-AKT and TP53 pathways, thereby influencing cellular sensitivity to DNA-damaging agents. These findings suggest that LincRNA-BC7 is a key determinant of the aggressive TNBC phenotype and the response to PARP inhibition. Our study establishes the LincRNA-BC7\/miR-663a axis as a novel biomarker for precision risk stratification and a promising therapeutic target to enhance treatment outcomes in BRCA1-associated breast cancers.<\/jats:p>","DOI":"10.3390\/epigenomes10020034","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:11:01Z","timestamp":1780333861000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LincRNA-BC7 as a Modulator of Olaparib Sensitivity in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8449-4727","authenticated-orcid":false,"given":"Olalekan Olatunde","family":"Fadebi","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Hatfield, Pretoria 0028, South Africa"},{"name":"SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babatunde Adebola","family":"Alabi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Hatfield, Pretoria 0028, South Africa"},{"name":"SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Khanyile","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Hatfield, Pretoria 0028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-3646","authenticated-orcid":false,"given":"Zodwa","family":"Dlamini","sequence":"additional","affiliation":[{"name":"SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5050-7350","authenticated-orcid":false,"given":"Rahaba","family":"Marima","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Hatfield, Pretoria 0028, South Africa"},{"name":"SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield, Pretoria 0028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3892\/br.2013.187","article-title":"Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)","volume":"2","author":"Zhang","year":"2014","journal-title":"Biomed. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Freihat, O., Sipos, D., and Kovacs, A. (2025). Global burden and projections of breast cancer incidence and mortality to 2050: A comprehensive analysis of GLOBOCAN data. Front Public Health, 13.","DOI":"10.3389\/fpubh.2025.1622954"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Crestani Morassutti, G., and Zanetti, M. (2026). Triple-negative breast cancer, pregnancy, and HLA alloreactivity: A cause for concern?. Front. Oncol., 16.","DOI":"10.3389\/fonc.2026.1806495"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kretzmann, H.G., and Adeniyi, O.V. (2025). Clinicopathological and molecular subtypes of breast cancer in the Eastern Cape, South Africa: A two-year retrospective study. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0325387"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"a3247","DOI":"10.4102\/SAJR.v29i1.3247","article-title":"Triple-negative breast cancer at Helen Joseph Hospital: Prevalence, age and imaging features","volume":"29","author":"Zondi","year":"2025","journal-title":"S. Afr. J. Radiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e021889","DOI":"10.1136\/bmjgh-2025-021889","article-title":"Time to diagnosis for breast, cervical and colorectal cancer in Zimbabwe and South Africa: A cross-sectional study","volume":"11","author":"Moodley","year":"2026","journal-title":"BMJ Global Health"},{"key":"ref_7","first-page":"1568","article-title":"Breast cancer in low-middle income countries: Abnormality in splicing and lack of targeted treatment options","volume":"10","author":"Francies","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s10549-016-4019-1","article-title":"Investigation of breast cancer sub-populations in black and white women in South Africa","volume":"160","author":"Dickens","year":"2016","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41523-018-0059-5","article-title":"Disparities in breast cancer tumor characteristics, treatment, time to treatment, and survival probability among African American and white women","volume":"4","author":"Foy","year":"2018","journal-title":"npj Breast Cancer"},{"key":"ref_10","first-page":"35","article-title":"Breast cancer among women in sub-Saharan Africa: Prevalence and a situational analysis","volume":"9","author":"Cumber","year":"2017","journal-title":"S. Afr. J. Gynaecol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.1111\/bph.13211","article-title":"Therapeutic targets of triple-negative breast cancer: A review","volume":"172","author":"Jamdade","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xiong, N., Wu, H., and Yu, Z. (2024). Advancements and challenges in triple-negative breast cancer: A comprehensive review of therapeutic and diagnostic strategies. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1405491"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1172\/JCI45014","article-title":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","volume":"121","author":"Lehmann","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41580-022-00566-8","article-title":"Long non-coding RNAs: Definitions, functions, challenges and recommendations","volume":"24","author":"Mattick","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00424-021-02641-z","article-title":"Long non-coding RNAs: Novel regulators of cellular physiology and function","volume":"474","author":"Oo","year":"2022","journal-title":"Pflug. Arch."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nrc.2017.99","article-title":"Non-coding RNA networks in cancer","volume":"18","author":"Anastasiadou","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gao, W., Sun, L., Gai, J., Cao, Y., and Zhang, S. (2024). Exploring the resistance mechanism of triple-negative breast cancer to paclitaxel through the scRNA-seq analysis. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0297260"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"zcab013","DOI":"10.1093\/narcan\/zcab013","article-title":"Cancer LncRNA Census 2 (CLC2): An enhanced resource reveals clinical features of cancer lncRNAs","volume":"3","author":"Vancura","year":"2021","journal-title":"NAR Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.ccell.2016.03.010","article-title":"Long Noncoding RNAs in Cancer Pathways","volume":"29","author":"Schmitt","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s43042-024-00553-y","article-title":"A brief review of noncoding RNA","volume":"25","author":"George","year":"2024","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41419-020-02954-4","article-title":"The roles of long noncoding RNAs in breast cancer metastasis","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fadebi, O.O., Miya, T.V., Khanyile, R., Dlamini, Z., and Marima, R. (2025). Long Intergenic Non-Coding RNAs and BRCA1 in Breast Cancer Pathogenesis: Neighboring Companions or Nemeses?. Noncoding RNA, 11.","DOI":"10.3390\/ncrna11010009"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.ajhg.2013.10.022","article-title":"Genetic and epigenetic regulation of human lincRNA gene expression","volume":"93","author":"Popadin","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ding, X., Zhu, L., Ji, T., Zhang, X., Wang, F., Gan, S., Zhao, M., and Yang, H. (2014). Long Intergenic Non-Coding RNAs (LincRNAs) Identified by RNA-Seq in Breast Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103270"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.molonc.2011.07.001","article-title":"The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing up the misunderstandings","volume":"5","author":"Helleday","year":"2011","journal-title":"Mol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xie, T., Dickson, K.-A., Yee, C., Ma, Y., Ford, C.E., Bowden, N.A., and Marsh, D.J. (2022). Targeting Homologous Recombination Deficiency in Ovarian Cancer with PARP Inhibitors: Synthetic Lethal Strategies That Impact Overall Survival. Cancers, 14.","DOI":"10.3390\/cancers14194621"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/bcp.12761","article-title":"Olaparib","volume":"81","author":"Goulooze","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_28","first-page":"3223","article-title":"Antitumor effects and mechanisms of olaparib in combination with carboplatin and BKM120 on human triple-negative breast cancer cells","volume":"40","author":"Zhao","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"904","DOI":"10.3332\/ecancer.2019.904","article-title":"Women\u2019s cancers: How the discovery of BRCA genes is driving current concepts of cancer biology and therapeutics","volume":"13","author":"Murthy","year":"2019","journal-title":"ecancer"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Schettini, F., Corona, S.P., Giudici, F., Strina, C., Sirico, M., Bernocchi, O., Milani, M., Ziglioli, N., Aguggini, S., and Azzini, C. (2021). Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.686776"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12347","DOI":"10.3390\/s120912347","article-title":"Multiple Applications of Alamar Blue as an Indicator of Metabolic Function and Cellular Health in Cell Viability Bioassays","volume":"12","author":"Rampersad","year":"2012","journal-title":"Sensors"},{"key":"ref_32","first-page":"1","article-title":"Basic Colorimetric Proliferation Assays: MTT, WST, and Resazurin","volume":"1601","author":"Engelhardt","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1126\/science.aam7344","article-title":"PARP inhibitors: Synthetic lethality in the clinic","volume":"355","author":"Lord","year":"2017","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Soetomo, S.A., Sharp, M.F., and Crismani, W. (2025). Differential PARP inhibitor responses in BRCA1-deficient and resistant cells in competitive co-culture. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0332860"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cell.2011.07.014","article-title":"A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?","volume":"146","author":"Salmena","year":"2011","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/nature09144","article-title":"A coding-independent function of gene and pseudogene mRNAs regulates tumour biology","volume":"465","author":"Poliseno","year":"2010","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4172\/2168-9296.1000158","article-title":"Slaughters Field Cancerization Concept of Carcinogenesis: The Path Forward to Early Cancer Detection and Chemoprevention","volume":"4","author":"Dakubo","year":"2015","journal-title":"Cell Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1002\/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q","article-title":"Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin","volume":"6","author":"Slaughter","year":"1953","journal-title":"Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1101\/gad.270959.115","article-title":"Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss","volume":"30","author":"Arun","year":"2016","journal-title":"Genes. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"188502","DOI":"10.1016\/j.bbcan.2021.188502","article-title":"Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer","volume":"1875","author":"Goyal","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"}],"container-title":["Epigenomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4655\/10\/2\/34\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:18:34Z","timestamp":1780978714000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4655\/10\/2\/34"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":40,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["epigenomes10020034"],"URL":"https:\/\/doi.org\/10.3390\/epigenomes10020034","relation":{},"ISSN":["2075-4655"],"issn-type":[{"value":"2075-4655","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]}}}