LncRNAs regulates cell death in osteosarcoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Osteosarcoma (OS) prognosis remains poor, necessitating novel therapeutic targets.
• Non-apoptotic receptor-mediated cell death (RCD) and long non-coding RNAs (lncRNAs) are implicated in OS pathogenesis.
• The role of lncRNAs in non-apoptotic RCD in OS is currently unexplored.

Purpose of the Study:

• To identify a functional lncRNA-based gene signature regulating non-apoptotic RCD in osteosarcoma.
• To investigate the prognostic value of this lncRNA signature.
• To explore the therapeutic potential of targeting these lncRNAs.

Main Methods:

• Systematic screening of immune-related lncRNAs associated with ferroptosis, necroptosis, and pyroptosis.
• Utilized Pearson correlation, univariate Cox regression, and machine learning algorithms (SVM, Random Forest, GLM) for lncRNA selection.
• Validated lncRNA function through in vitro assays and analyzed immune infiltration using CIBERSORT.

Main Results:

• A prognostic risk model comprising four lncRNAs (AC006033.2, AC124798.1, LINC01517, L3MBTL4-AS1) was constructed with high predictive accuracy (AUCs up to 0.881).
• The high-risk group showed a worse prognosis, with distinct immune infiltration patterns.
• Silencing LINC01517 inhibited proliferation and modulated pyroptosis, ferroptosis, and necroptosis in OS cells.

Conclusions:

• A novel lncRNA signature associated with non-apoptotic RCD has been identified in osteosarcoma.
• This signature serves as a reliable prognostic biomarker for osteosarcoma patients.
• Targeting specific lncRNAs, such as LINC01517, presents a promising therapeutic strategy for osteosarcoma.