{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:56:46Z","timestamp":1790600206184,"version":"4.1.0"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"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>Cancer claims nearly 10 million lives yearly, demanding innovative diagnostics and therapies beyond surgery and chemotherapy\u2019s limitations, such as resistance and toxicity. Next-generation sequencing has unveiled PIWI-interacting RNAs (piRNAs), 26\u201331 nucleotide small non-coding RNAs, as pivotal regulators in cancer pathogenesis, offering fresh biomarkers and targets from a molecular biosciences lens. Once deemed germline-exclusive for transposon silencing via PIWI proteins (PIWIL1-4), piRNAs exhibit somatic dysregulation across malignancies, driving hallmarks like proliferation, metastasis, and chemoresistance. In colorectal cancer, piR-823 fosters invasion by stabilizing HIF-1\u03b1 and G6PD, correlating with poor prognosis. Gastric cancers overexpress piR-651, promoting G2\/M arrest evasion; lung cancers feature PMLCPIR enhancing ITGB1-PI3K-AKT signaling; multiple myeloma leverages piR-823 for proliferation; and hepatocellular carcinoma shows PIWIL1 upregulation tied to stemness. PiRNAs\u2019 tissue-specific signatures enable liquid biopsy detection, with panels predicting recurrence-free survival (e.g., piR-54265\/STAT3 axis in CRC). Therapeutically, piRNA mimics\/inhibitors (e.g., LNA-antisense against piR-L-138 in lung squamous cell carcinoma) sensitize tumors to cisplatin, while PIWI knockdown curbs metastasis preclinically. This review dissects piRNA biogenesis, oncogenic\/suppressive duality, and translational promise. By bridging molecular mechanisms to clinical utility, encompassing diagnostics via plasma profiling and therapeutics like nanoparticle-delivered piRNA therapeutics, piRNAs herald a paradigm shift in precision oncology.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1775335","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:16:14Z","timestamp":1775535374000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Emerging roles of PIWI-interacting RNAs in cancer molecular diagnostics and therapeutics: a molecular biosciences perspective"],"prefix":"10.3389","volume":"13","author":[{"given":"Qianqian","family":"Yang","sequence":"first","affiliation":[{"name":"Clinical Medical College, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Aesthetics, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Su","sequence":"additional","affiliation":[{"name":"Hangzhou Heyunjia Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e33767","DOI":"10.1016\/j.heliyon.2024.e33767","article-title":"PIWI-interacting RNAs (PiRNAs) as emerging biomarkers and therapeutic targets in biliary tract cancers: a comprehensive review","volume":"10","author":"Ahmadi","year":"2024","journal-title":"Heliyon"},{"key":"B2","doi-asserted-by":"publisher","first-page":"153757","DOI":"10.1016\/j.prp.2021.153757","article-title":"piRNA: a promising biomarker in early detection of gastrointestinal cancer","volume":"230","author":"Ameli","year":"2022","journal-title":"Pathol. 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