{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:42:24Z","timestamp":1783489344457,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Poland","award":["2016\/21\/B\/NZ4\/00202"],"award-info":[{"award-number":["2016\/21\/B\/NZ4\/00202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Infertility due to ovarian toxicity is a common side effect of cancer treatment in premenopausal women. Tamoxifen (TAM) is a selective estrogen receptor modulator that prevented radiation- and chemotherapy-induced ovarian failure in preclinical studies. In the current study, we examined the potential regulatory role of long noncoding RNAs (lncRNAs) in the mechanism of action of TAM in the ovaries of tumor-bearing rats receiving cyclophosphamide (CPA) as cancer therapy. We identified 166 lncRNAs, among which 49 were demonstrated to be differentially expressed (DELs) in the ovaries of rats receiving TAM and CPA compared to those receiving only CPA. A total of 24 DELs were upregulated and 25 downregulated by tamoxifen. The identified DELs shared the characteristics of noncoding RNAs described in other reproductive tissues. Eleven of the identified DELs displayed divergent modes of action, regulating target transcripts via both cis- and trans-acting pathways. Functional enrichment analysis revealed that, among target genes ascribed to the identified DELs, the majority were involved in apoptosis, cell adhesion, immune response, and ovarian aging. The presented data suggest that the molecular mechanisms behind tamoxifen\u2019s protective effects in the ovaries may involve lncRNA-dependent regulation of critical signaling pathways related to inhibition of follicular transition and ovarian aging, along with the suppression of apoptosis and regulation of cell adhesion. Employing a tumor-bearing animal model undergoing chemotherapy, which accurately reflects the conditions of mammary cancer, reinforces the obtained results. Given that tamoxifen remains a key player in the management and prevention of breast cancer, understanding its ovarian-specific actions in cancer patients is crucial and requires detailed functional studies to clarify the underlying molecular mechanisms.<\/jats:p>","DOI":"10.3390\/ijms252312538","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T04:21:36Z","timestamp":1732249296000},"page":"12538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Role of lncRNAs in the Protective Action of Tamoxifen on the Ovaries of Tumor-Bearing Rats Receiving Cyclophosphamide"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2287-3243","authenticated-orcid":false,"given":"Sylwia","family":"Swigonska","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Warmia and Mazury in Olsztyn, Prawochenskiego 5, 10-720 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-6148","authenticated-orcid":false,"given":"Anna","family":"Nynca","sequence":"additional","affiliation":[{"name":"Department of Animal Anatomy and Physiology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Molcan","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Petroff","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824-1314, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6896-5023","authenticated-orcid":false,"given":"Renata E.","family":"Ciereszko","sequence":"additional","affiliation":[{"name":"Department of Animal Anatomy and Physiology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/s41571-022-00672-8","article-title":"Is Early-Onset Cancer an Emerging Global Epidemic? 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