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Long non-coding RNA AC133552.2: biomarker and therapeutic target in osteosarcoma via PANoptosis gene screening
Wenrui Zhao1,2,3, Yameng Wang1,2,3, Junchao Zhu1,2,3
1Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
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.
Insights
This study identifies long non-coding RNAs (lncRNAs) involved in PANoptosis, a cell death process, to predict outcomes in osteosarcoma. The lncRNA AC133552.2 shows promise as a biomarker and therapeutic target for this bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma is a primary bone cancer in children and adolescents with poor survival rates due to metastasis and recurrence.
- PANoptosis, a cell death pathway involving pyroptosis, apoptosis, and necroptosis, is implicated in cancer progression.
Purpose of the Study:
- To investigate the role of PANoptosis-related genes (PRGs) and long non-coding RNAs (lncRNAs) in osteosarcoma.
- To develop a prognostic model for osteosarcoma based on PRGs and lncRNAs.
Main Methods:
- Bioinformatics analysis of RNA expression data from GEO and TARGET databases.
- Identification of differentially expressed genes (DEGs) and PRGs.
- Co-expression analysis to link lncRNAs with PRGs and construct a risk prognostic model.
Main Results:
- A prognostic model comprising five PRGs and two lncRNAs demonstrated high predictive accuracy (AUCs 0.876, 0.787, 0.794 for 1, 3, 5 years).
- lncRNA AC133552.2 was significantly downregulated in osteosarcoma, correlating with poor prognosis and reduced immune infiltration.
- AC133552.2 manipulation affected osteosarcoma cell proliferation, migration, and tumor growth in xenograft models.
Conclusions:
- lncRNA AC133552.2 is a potential prognostic biomarker and therapeutic target for osteosarcoma.
- Further research is warranted to elucidate the molecular mechanisms and clinical applications of AC133552.2 in osteosarcoma treatment.
