Exosome-Derived LncRNA MIR4435-2HG Suppresses Malignant Phenotypes and Brain Metastasis in Small Cell Lung Cancer

Background:Brain metastasis in small cell lung cancer(SCLC) is a significant factor leading to poor prognosis in patients.To investigate the role of exosomal lncRNA MIR4435-2HG in the development and progression of brain metastasis in small cell lung cancer , and its effects on malignant phenotypes including proliferation, migration, and invasion in Small Cell Lung Cancer . Methods:Transcriptome sequencing and bioinformatics analysis were utilized to identify key candidate lncRNAs in Small Cell Lung Cancer, followed by Gene ontology analysis and Pathway analysis. The expression of exosomal lncRNA MIR4435-2HG was measured using quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assay, and its clinicopathological characteristics were analyzed. Following the assessment of cellular exosome uptake via confocal fluorescence microscopy, the effects of exosomal lncRNA MIR4435-2HG overexpression on proliferation, invasion, and migration in small cell lung cancer cells were evaluated using Cell Counting Kit-8 (CCK-8), colony formation assay, Transwell migration and invasion assays, and scratch assay. Results:Transcriptome sequencing combined with database analysis revealed differential expression of exosomal lncRNA MIR4435-2HG in Small Cell Lung Cancer patients and small cell lung cancer patients with brain metastasis. Gene ontology analysis predicted its enrichment in focal adhesion and cell-matrix adhesion processes, while subsequent kyoto encyclopedia of genes and genomes pathway analysis demonstrated its close association with cancer-related proteoglycan signaling pathways. RT-qPCR and tissue fluorescence in situ hybridization assays confirmed that exosomal lncRNA MIR4435-2HG exhibits low expression in plasma exosomes, extracellular vesicles, and tissues of patients with small cell lung cancer and small cell lung cancer brain metastasis; this low expression correlates with the clinical stage of small cell lung cancer and brain metastasis. Furthermore, overexpression of exosome-derived lncRNA MIR4435-2HG suppressed the proliferation, migration, and invasion of small cell lung cancer cells. Conclusion:Exosomal lncRNA MIR4435-2HG inhibits malignant phenotypes in small cell lung cancer and suppresses brain metastasis.