{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:08:25Z","timestamp":1789463305414,"version":"build-2803163510"},"reference-count":267,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Metastatic prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men globally. This is largely attributable to the occurrence of therapeutic resistance that reduces the efficacy of the traditional treatment, such as Androgen deprivation therapy, chemotherapy, and radiotherapy. Accumulating evidence suggests that prostate cancer stem cells a rare population of Cancer Stem Cells drive therapy resistance by sustaining self-renewal, tumor plasticity, epithelial-mesenchymal transition, and metastasis. Concurrently, miRNAs are critical post-transcriptional regulators of gene expression, modulating key signalling pathways that control CSC stemness, reshaping tumor microenvironment, and conferring resistance to therapy. Dysregulation of miRNAs has been closely associated with the regulation of CSCs and the progression of metastatic PCa, and causes disease recurrence. In accordance with their targets, miRNAs can function either as oncogenic drivers that promote cancer progression or as tumor suppressors that inhibit malignant transformation and growth. Moreover, it contributes to the capacity of CSCs to withstand therapy and initiate disease recurrence. Recent advances in precision oncology have increased the pace of novel therapeutic modalities, such as CRISPR\/Cas9, nanotechnology-based delivery vehicles, chimeric antigen receptor -T cell therapy, and epigenetic reprogramming strategies to counteract aberrant transcriptional states that sustain PCSC plasticity. The integration of these approaches offers a promising strategy to overcome refractoriness to treatment and improve clinical outcomes in advanced PCa. This review highlights the complex interplay between miRNAs and PCSCs in therapy resistance of metastatic PCa, and explores their translational potential in shaping durable and more effective clinical interventions.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1904473","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:08:55Z","timestamp":1789459735000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unravelling therapeutic resistance: role of cancer stem cell and microRNA in metastatic prostate cancer"],"prefix":"10.3389","volume":"13","author":[{"given":"Hitakshi","family":"Moondra","sequence":"first","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences","place":["Jodhpur, Rajasthan, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam Ram","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Department of Urology, All India Institute of Medical Sciences","place":["Jodhpur, Rajasthan, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh Kumar","family":"Ahirwar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology","place":["Jodhpur, Rajasthan, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mithu","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences","place":["Jodhpur, Rajasthan, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surendra Kumar","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Oncology Science, University of Oklahoma Health Sciences Centre","place":["Oklahoma City, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamla Kant","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences","place":["Jodhpur, Rajasthan, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3567","DOI":"10.1007\/s11033-021-06387-w","article-title":"Sonic hedgehog signaling is associated with resistance to zoledronic acid in CD133high\/CD44high prostate cancer stem cells","volume":"48","author":"Acikgoz","year":"2021","journal-title":"Mol. 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