{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:08:00Z","timestamp":1784632080613,"version":"3.55.0"},"reference-count":39,"publisher":"Scientific Scholar","content-domain":{"domain":["cytojournal.com"],"crossmark-restriction":true},"short-container-title":["Cytojournal"],"abstract":"\n Objective:<\/jats:title>\n While carboplatin remains a cornerstone chemotherapeutic agent for ovarian carcinoma, the emergence of resistance constitutes a major contributor to therapeutic failure and compromised clinical outcomes. This study elucidates molecular mechanisms driving carboplatin resistance and identifies novel therapeutic targets for carboplatin-refractory malignancies through characterization of a long non-coding RNA (lncRNA)-encoded micropeptide.<\/jats:p>\n <\/jats:sec>\n \n Material and Methods:<\/jats:title>\n Ribosome profiling analysis delineated translational alterations induced by carboplatin in ovarian cancer models. Mechanistic validation was achieved through the integration of gain- and loss-of-function methodologies, nuclear localization assays, and quantitative assessment of deoxyribonucleic acid (DNA) damage through enumeration of gamma-H2AX (phosphorylated histone H2AX at serine 139) foci, supplemented by alkaline comet analysis. The therapeutic significance was corroborated using subcutaneous xenograft models derived from patient-derived ovarian cancer cells.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The micropeptide carboplatin-induced upregulation factor (CARUF), derived from lncRNA LOC101926915, was markedly upregulated in response to carboplatin treatment, with ribosome profiling showing significant enrichment of ribosome-associated LOC101926915 transcripts (adjusted\n P<\/jats:italic>\n < 0.01 and log2FC >1). In clinical specimens, elevated CARUF expression was positively correlated with platinum resistance (r = 0.425,\n P<\/jats:italic>\n < 0.001). Functional analyses showed that CARUF overexpression promoted DNA damage repair (\n P<\/jats:italic>\n < 0.001) and enhanced carboplatin resistance both\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n (\n P<\/jats:italic>\n < 0.001). In contrast, CARUF inhibition impaired DNA damage repair (\n P<\/jats:italic>\n < 0.001) and restored carboplatin sensitivity (\n P<\/jats:italic>\n < 0.001), resulting in reduced cell viability\n in vitro<\/jats:italic>\n (\n P<\/jats:italic>\n < 0.001) and suppressed tumor growth\n in vivo<\/jats:italic>\n (\n P<\/jats:italic>\n < 0.001). Mechanistically, carboplatin-induced DNA lesions activated ataxia-telangiectasia mutated and Rad3-related (ATR) kinase, which phosphorylated CARUF, facilitated its localization to DNA lesion sites, and enhanced DNA repair capacity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Our findings identify CARUF as a critical mediator of aberrant DNA damage response signaling in carboplatin-resistant ovarian cancer, indicating its potential as a druggable target for overcoming carboplatin resistance.<\/jats:p>\n <\/jats:sec>","DOI":"10.25259\/cytojournal_99_2025","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:32:01Z","timestamp":1784629921000},"page":"44","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long non-coding RNA LOC101926915-encoded micropeptide carboplatin-induced upregulation factor confers carboplatin resistance in ovarian cancer"],"prefix":"10.25259","volume":"23","author":[{"given":"Man","family":"Li","sequence":"first","affiliation":[{"name":"Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YingRu","family":"Xu","sequence":"additional","affiliation":[{"name":"Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiBiao","family":"Mai","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences, Hong Kong, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Ren","sequence":"additional","affiliation":[{"name":"Clinical Experimental Center, Jiangmen Key Laboratory of Clinical Biobanks and Translational Research, Jiangmen Central Hospital, Jiangmen, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Guangzhou, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SuWen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Guangzhou, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZunFu","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 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