{"title":"hsa_circ_0005963 downregulation suppresses NSCLC malignant progression by miR-506-3p/SOX9-mediated stemness regulation.","authors":"Xuechao Zhou, Yu Yao, Huaiyin Ding","doi":"10.1080/17501911.2026.2654577","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated the role and regulatory mechanisms underlying hsa_circ_0005963 in NSCLC.</p><p><strong>Methods: </strong>FISH and RT-qPCR were used to assess hsa_circ_0005963 expression in NSCLC cells and tissues. Dual-luciferase reporter assay was employed to characterize hsa_circ_0005963 downstream targets. Transwell migration and EdU incorporation were performed to detect NSCLC cell proliferation and migration. A mouse tumor xenograft model was constructed to assess hsa_circ_0005963 functions in NSCLC metastasis and progressions.</p><p><strong>Results: </strong>hsa_circ_0005963 expression was upregulated in NSCLC tissues and cells. High hsa_circ_0005963 expression indicates poor prognosis, including overall survival. hsa_circ_0005963 silencing inhibited NSCLC proliferation and migration. Experiments confirmed that hsa_circ_0005963 downregulation suppresses A549 tumor invasions. A dual-luciferase reporter assay identified SOX9 and microRNA as hsa_circ_0005963 downstream targets, which was validated by RT-qPCR. SOX9 overexpression or miR-506-3p downregulation reversed the hsa_circ_0005963 silencing inhibitory effects upon proliferation and migrations. SOX9 overexpression reversed miR-506-3p effects to inhibit proliferation and migration in both cell lines.</p><p><strong>Conclusion: </strong>hsa_circ_0005963 promotes NSCLC development by sponging miR-506-3p to enhance SOX9 expression.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"565-573"},"PeriodicalIF":3.1000,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215287/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17501911.2026.2654577","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/5/21 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: This study investigated the role and regulatory mechanisms underlying hsa_circ_0005963 in NSCLC.
Methods: FISH and RT-qPCR were used to assess hsa_circ_0005963 expression in NSCLC cells and tissues. Dual-luciferase reporter assay was employed to characterize hsa_circ_0005963 downstream targets. Transwell migration and EdU incorporation were performed to detect NSCLC cell proliferation and migration. A mouse tumor xenograft model was constructed to assess hsa_circ_0005963 functions in NSCLC metastasis and progressions.
Results: hsa_circ_0005963 expression was upregulated in NSCLC tissues and cells. High hsa_circ_0005963 expression indicates poor prognosis, including overall survival. hsa_circ_0005963 silencing inhibited NSCLC proliferation and migration. Experiments confirmed that hsa_circ_0005963 downregulation suppresses A549 tumor invasions. A dual-luciferase reporter assay identified SOX9 and microRNA as hsa_circ_0005963 downstream targets, which was validated by RT-qPCR. SOX9 overexpression or miR-506-3p downregulation reversed the hsa_circ_0005963 silencing inhibitory effects upon proliferation and migrations. SOX9 overexpression reversed miR-506-3p effects to inhibit proliferation and migration in both cell lines.
Conclusion: hsa_circ_0005963 promotes NSCLC development by sponging miR-506-3p to enhance SOX9 expression.
期刊介绍:
Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community.
Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.