{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:19:20Z","timestamp":1788265160464,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shandong Provincial Medical and Health Commission","award":["202305031628"],"award-info":[{"award-number":["202305031628"]}]},{"name":"Shandong Provincial Medical and Health Commission","award":["202105011064"],"award-info":[{"award-number":["202105011064"]}]},{"name":"Shandong Provincial Maternal and Child Health Care Association","award":["SFYZXJJ-2024035"],"award-info":[{"award-number":["SFYZXJJ-2024035"]}]},{"name":"Shandong Provincial Maternal and Child Health Care Association","award":["SFYXH-2025Y015"],"award-info":[{"award-number":["SFYXH-2025Y015"]}]},{"name":"Shandong Provincial Maternal and Child Health Care Hospital","award":["2021SFF045"],"award-info":[{"award-number":["2021SFF045"]}]},{"name":"Shandong Provincial Maternal and Child Health Care Hospital","award":["2021RS"],"award-info":[{"award-number":["2021RS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Ovarian cancer is one of the most lethal gynecological malignancies worldwide, largely due to late diagnosis and rapid disease progression. Increasing evidence suggests that dysregulation of calcium-binding proteins and microRNA-mediated regulatory networks contributes to ovarian cancer progression. However, the role of S100A6 and its upstream regulatory mechanisms in ovarian cancer remain poorly understood. Methods: S100A6 expression in ovarian cancer cell lines and tissues was assessed by transcriptome sequencing, qPCR, and immunohistochemistry. Functional assays (CCK-8, EdU, Transwell, wound-healing, flow cytometry) and a xenograft model were used to evaluate S100A6 effects. Bioinformatic analysis, dual-luciferase reporter assays, and rescue experiments identified upstream miRNAs. JAK-STAT involvement was examined by Western blot. Survival analysis was performed using Kaplan\u2013Meier Plotter. Results: S100A6 expression was significantly upregulated in ovarian cancer cells and tumor tissues compared with normal controls. Silencing S100A6 inhibited cell proliferation, migration, and invasion while promoting apoptosis in vitro and suppressed tumor growth in vivo. Mechanistically, S100A6 activated the JAK\u2013STAT pathway, and pharmacological inhibition of STAT3 with Stattic reversed S100A6-promoted migration. Further analyses identified Let-7c-3p as a direct upstream regulator of S100A6. Let-7c-3p bound to the 3\u2032-UTR of S100A6 and suppressed its expression, thereby reversing S100A6-mediated oncogenic phenotypes and inhibiting JAK-STAT signaling. Survival analysis revealed that elevated S100A6 expression was associated with shorter progression-free survival in ovarian cancer patients. Conclusions: Our findings identify a novel Let-7c-3p\/S100A6\/JAK-STAT regulatory axis that promotes ovarian cancer progression. This study provides new insights into the molecular mechanisms underlying ovarian cancer development and suggests that targeting this regulatory network may represent a potential therapeutic strategy.<\/jats:p>","DOI":"10.3390\/cancers18172834","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:33:32Z","timestamp":1788262412000},"page":"2834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Let-7c-3p Suppresses Ovarian Cancer Progression by Targeting S100A6 and Inhibiting JAK-STAT Signaling"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-5632","authenticated-orcid":false,"given":"Bing","family":"Yuan","sequence":"first","affiliation":[{"name":"Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, Jinan 250021, China"},{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Xiaoyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"given":"Yujie","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Hang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"given":"Yuli","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Panpan","family":"Bei","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-6746","authenticated-orcid":false,"given":"Jidong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Mingyong","family":"Han","sequence":"additional","affiliation":[{"name":"Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12943-024-01967-3","article-title":"Drug resistance in ovarian cancer: From mechanism to clinical trial","volume":"23","author":"Wang","year":"2024","journal-title":"Mol. 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