{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:06:12Z","timestamp":1784786772977,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Platinum-based chemotherapy remains the cornerstone of ovarian cancer treatment, yet acquired resistance severely limits efficacy. Because platinum agents can also influence immunogenic cell death and tumor microenvironment (TME) remodeling, clarifying cellular pharmacological mechanisms of sensitivity and resistance within the ovarian cancer tumor ecosystem is important for understanding therapeutic failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated single-cell RNA-seq from treatment-na\u00efve and post-neoadjuvant chemotherapy ovarian tumors with bulk multi-omics cohorts to map epithelial tumor heterogeneity, transcriptional reprogramming, pathway activation, immune infiltration, and inferred cell\u2013cell communication networks. DUSP5 was identified as a candidate regulator linked to stress-adaptive programs. Functional validation included qPCR, proliferation, migration, colony-formation, carboplatin dose-response, and xenograft assays following stable DUSP5 knockdown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Single-cell analysis revealed chemotherapy-associated epithelial states with enhanced stress, EMT, hypoxia, and inflammatory signatures. Elevated DUSP5 expression correlated with MAPK\/JAK-STAT\/TGF-\u03b2 signaling, myeloid\/stromal infiltration, and clinical outcome differences in independent cohorts. DUSP5 depletion suppressed proliferation and migration, amplified carboplatin-induced MAPK transcriptional responses and pro-apoptotic signaling (BAX\/PUMA upregulation, BCL2 downregulation), reduced IC50 values in both OVCAR8 and SKOV3 cells, and significantly inhibited xenograft tumor growth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DUSP5 may contribute to platinum response and resistance by linking tumor-intrinsic adaptive programs with TME-associated features in ovarian cancer. These findings support DUSP5 as a candidate biomarker and therapeutic target that warrants further mechanistic and clinical validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1842271","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:39:20Z","timestamp":1784785160000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["DUSP5 contributes to platinum resistance in ovarian cancer: single-cell discovery and functional validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Chengfeng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oncology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wehua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Luzhou People\u2019s Hospital","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjun","family":"Liao","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Center for Gynecology and Breast Diseases (Gynecology), Affiliated Hospital of Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyi","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Center for Gynecology and Breast Diseases (Gynecology), Affiliated Hospital of Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.bbagen.2018.11.005","article-title":"Mechanisms underlying acquired platinum resistance in high grade serous ovarian cancer - a mini review","volume":"1863","author":"Binju","year":"2019","journal-title":"Biochim. 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