Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening

Abstract Osteosarcoma, the most common primary bone cancer in children and adolescents, presents significant challenges, particularly in metastasis and recurrence, resulting in poor survival rates. This study explores the role of PANoptosis—a complex cell death mechanism involving pyroptosis, apopto...

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Main Authors: Wenrui Zhao, Yameng Wang, Junchao Zhu, Shahrzad Arya, Guowen Huang, Shengqin Li, Qi Chen, Xijuan Liu, Jinghong Yuan, Jingyu Jia
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-93167-2
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author Wenrui Zhao
Yameng Wang
Junchao Zhu
Shahrzad Arya
Guowen Huang
Shengqin Li
Qi Chen
Xijuan Liu
Jinghong Yuan
Jingyu Jia
author_facet Wenrui Zhao
Yameng Wang
Junchao Zhu
Shahrzad Arya
Guowen Huang
Shengqin Li
Qi Chen
Xijuan Liu
Jinghong Yuan
Jingyu Jia
author_sort Wenrui Zhao
collection DOAJ
description Abstract Osteosarcoma, the most common primary bone cancer in children and adolescents, presents significant challenges, particularly in metastasis and recurrence, resulting in poor survival rates. This study explores the role of PANoptosis—a complex cell death mechanism involving pyroptosis, apoptosis, and necroptosis—in osteosarcoma by identifying relevant long non-coding RNAs (lncRNAs) and their prognostic significance. Bioinformatics analyses used RNA expression data from the GEO and TARGET databases to identify differentially expressed genes (DEGs) and PANoptosis-related genes (PRGs). Co-expression analysis revealed lncRNAs linked to PRGs, forming a risk prognostic model. Five PRGs and two lncRNAs were significantly associated with prognosis, with the model showing high predictive accuracy (AUC 0.876, 0.787, and 0.794 for 1, 3, and 5 years). Notably, lncRNA AC133552.2 was downregulated in osteosarcoma tissues, correlating with poor survival and reduced immune infiltration. Silencing AC133552.2 promoted cell proliferation and migration, while overexpression inhibited tumor growth and metastasis, confirmed in xenograft models. AC133552.2 emerges as a potential biomarker and therapeutic target, with future research needed to explore its molecular mechanisms and clinical application.
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spelling doaj-art-0b2545cb8bc34f51aef2c0e92f99ef612025-08-20T02:41:31ZengNature PortfolioScientific Reports2045-23222025-03-0115111610.1038/s41598-025-93167-2Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screeningWenrui Zhao0Yameng Wang1Junchao Zhu2Shahrzad Arya3Guowen Huang4Shengqin Li5Qi Chen6Xijuan Liu7Jinghong Yuan8Jingyu Jia9Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Surgery, Cedars-Sinai Medical CenterDepartment of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Nanchang UniversityDepartment of Pediatrics, The Second Affiliated Hospital of Nanchang UniversityDepartment of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityAbstract Osteosarcoma, the most common primary bone cancer in children and adolescents, presents significant challenges, particularly in metastasis and recurrence, resulting in poor survival rates. This study explores the role of PANoptosis—a complex cell death mechanism involving pyroptosis, apoptosis, and necroptosis—in osteosarcoma by identifying relevant long non-coding RNAs (lncRNAs) and their prognostic significance. Bioinformatics analyses used RNA expression data from the GEO and TARGET databases to identify differentially expressed genes (DEGs) and PANoptosis-related genes (PRGs). Co-expression analysis revealed lncRNAs linked to PRGs, forming a risk prognostic model. Five PRGs and two lncRNAs were significantly associated with prognosis, with the model showing high predictive accuracy (AUC 0.876, 0.787, and 0.794 for 1, 3, and 5 years). Notably, lncRNA AC133552.2 was downregulated in osteosarcoma tissues, correlating with poor survival and reduced immune infiltration. Silencing AC133552.2 promoted cell proliferation and migration, while overexpression inhibited tumor growth and metastasis, confirmed in xenograft models. AC133552.2 emerges as a potential biomarker and therapeutic target, with future research needed to explore its molecular mechanisms and clinical application.https://doi.org/10.1038/s41598-025-93167-2OsteosarcomaPANoptosisLong non-coding RNAAC133552.2Therapeutic target
spellingShingle Wenrui Zhao
Yameng Wang
Junchao Zhu
Shahrzad Arya
Guowen Huang
Shengqin Li
Qi Chen
Xijuan Liu
Jinghong Yuan
Jingyu Jia
Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening
Scientific Reports
Osteosarcoma
PANoptosis
Long non-coding RNA
AC133552.2
Therapeutic target
title Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening
title_full Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening
title_fullStr Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening
title_full_unstemmed Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening
title_short Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening
title_sort long non coding rna ac133552 2 biomarker and therapeutic target in osteosarcoma via panoptosis gene screening
topic Osteosarcoma
PANoptosis
Long non-coding RNA
AC133552.2
Therapeutic target
url https://doi.org/10.1038/s41598-025-93167-2
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