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Although some malignancies are manageable by a mix of chemotherapy, surgery, radiation, and targeted therapy, most malignant tumors either exhibit poor responsiveness to early identification or endure post-treatment survival. The prognosis for prostate cancer (PCa) is unfavorable since it is a perilous and lethal malignancy. The capacity of phytochemical and nutraceutical chemicals to repress oncogenic lncRNAs and activate tumor suppressor lncRNAs has garnered significant attention as a possible strategy to diminish the development, proliferation, metastasis, and invasion of cancer cells. A potential technique to treat cancer and enhance the sensitivity of cancer cells to existing conventional therapies is the use of phytochemicals with anticancer characteristics. Functional studies indicate that lncRNAs modulate drug resistance, stemness, invasion, metastasis, angiogenesis, and proliferation via interactions with tumor suppressors and oncoproteins. Among them, numerous lncRNAs, such as HOTAIR, PlncRNA1, GAS5, MEG3, LincRNA-21, and POTEF-AS1, support the development of PCa through many molecular mechanisms, including modulation of tumor suppressors and regulation of various signal pathways like PI3K\/Akt, Bax\/Caspase 3, P53, MAPK cascade, and TGF-\u03b21. Other lncRNAs, in particular, MALAT-1, CCAT2, DANCR, LncRNA-ATB, PlncRNA1, LincRNA-21, POTEF-AS1, ZEB1-AS1, SChLAP1, and H19, are key players in regulating the aforementioned processes. Natural substances have shown promising anticancer benefits against PCa by altering essential signaling pathways. The overexpression of some lncRNAs is associated with advanced TNM stage, metastasis, chemoresistance, and reduced survival. LncRNAs possess crucial clinical and transitional implications in PCa, as diagnostic and prognostic biomarkers, as well as medicinal targets. To impede the progression of PCa, it is beneficial to target aberrant long non-coding RNAs using antisense oligonucleotides or small interfering RNAs (siRNAs). This prevents them from transmitting harmful messages. In summary, several precision medicine approaches may be used to rectify dysfunctional lncRNA regulatory circuits, so improving early PCa detection and eventually facilitating the conquest of this lethal disease. Due to their presence in biological fluids and tissues, they may serve as novel biomarkers. Enhancing PCa treatments mitigates resistance to chemotherapy and radiation.<\/jats:p>","DOI":"10.1007\/s00210-024-03736-x","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T04:33:49Z","timestamp":1737174829000},"page":"6349-6368","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Natural products and long non-coding RNAs in prostate cancer: insights into etiology and treatment resistance"],"prefix":"10.1007","volume":"398","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2585-9957","authenticated-orcid":false,"given":"Hanan","family":"Elimam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Bakr","family":"Zaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai A.","family":"Abd-Elmawla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebatallah A.","family":"Darwish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Hatawsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora M.","family":"Aborehab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif S. 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