{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:09:01Z","timestamp":1783930141072,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Noncommunicable Chronic Diseases National Science and Technology Major Project","award":["2025ZD0545402"],"award-info":[{"award-number":["2025ZD0545402"]}]},{"name":"Youth Project of Shanghai Pudong New Area Health Talent Training Programs","award":["2024PDWSYCQN-02"],"award-info":[{"award-number":["2024PDWSYCQN-02"]}]},{"name":"Youth Project of Shanghai Pudong New Area Health Talent Training Programs","award":["2026PDWSYCQN-04"],"award-info":[{"award-number":["2026PDWSYCQN-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The diversity of RNA isoforms plays a critical role in regulating the development and progression of human cancers. Our previous work has demonstrated that piR-2158 exerts antitumor activity in breast cancer by repressing IL11-STAT3 signaling. Methods: The isoforms of piR-2158 were analyzed using Sanger sequencing, quantitative real-time PCR (qRT-PCR), and Gene Expression Omnibus (GEO) dataset. Cell proliferation capacity was assessed using Cell Counting Kit-8 (CCK-8) assays and Ki67 immunofluorescence staining. Cell migration was evaluated using wound healing assays. Cancer cell stemness was analyzed using mammosphere formation assay, stemness marker detection, and ALDH activity assay. Results: We identified two types of piR-2158 isoforms in mammary tissues: a 31 nt long isopiR (designated as iso-piR-2158-L) and a 28 nt short isopiR (designated as iso-piR-2158-S). Predominant expression of iso-piR-2158-L was observed in normal mammary epithelial cells and adjacent non-tumor breast tissues, whereas it was significantly downregulated in TNBC cell lines and primary tumor tissues. We experimentally demonstrated that iso-piR-2158-L and iso-piR-2158-S exert distinct effects on TNBC cell proliferation, migration, and stemness, with iso-piR-2158-L showing significantly stronger antitumor effects than iso-piR-2158-S. Subsequent mechanistic studies revealed that iso-piR-2158-L suppresses IL11 expression more effectively, compared to iso-piR-2158-S. Conclusions: Our findings reveal a piRNA isoform-based regulatory pathway that may be involved in regulating pathological transformation, tumor initiation, and progression in TNBC.<\/jats:p>","DOI":"10.3390\/cancers18142237","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:28:27Z","timestamp":1783927707000},"page":"2237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Novel piR-2158 Isoforms and Their Distinct Antitumor Effects on Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Zhongrui","family":"Wang","sequence":"first","affiliation":[{"name":"Medical Innovation Center and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China"},{"name":"Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Innovation Center and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China"},{"name":"Department of Ultrasound Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Qian","sequence":"additional","affiliation":[{"name":"Medical Innovation Center and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China"},{"name":"Department of  Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayuan","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Innovation Center and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4196-9662","authenticated-orcid":false,"given":"Zuoren","family":"Yu","sequence":"additional","affiliation":[{"name":"Medical Innovation Center and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-7137","authenticated-orcid":false,"given":"Qian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Medical Innovation Center and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"L\u00fc","sequence":"additional","affiliation":[{"name":"Medical Innovation Center and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41580-022-00528-0","article-title":"Emerging roles and functional mechanisms of PIWI-interacting RNAs","volume":"24","author":"Wang","year":"2023","journal-title":"Nat. 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