LINC02178 drives lung adenocarcinoma progression and serves as a therapeutic target for nanodelivery-based intervention

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Gene therapy has garnered significant attention in cancer treatment. Here, we identified the long noncoding RNA LINC02178 as an oncogenic driver in lung adenocarcinoma (LUAD) and developed a nanoparticle-based small interfering RNA delivery system (NPs/2178) targeting this gene, providing novel insights for gene therapy development. Bioinformatics analysis was used to identify LINC02178 as a candidate oncogene and evaluate its clinical value. Subcellular localization of LINC02178 was determined through cytoplasmic/nuclear RNA fractionation coupled withs Reverse transcription quantitative polymerase chain reaction (RT-qPCR). The transfection efficiency of the NPs was assessed using confocal microscopy and RT‒qPCR. The biological toxicity of NPs/2178 was tested via cell Counting Kit-8 (CCK-8) and live/dead assays. Flow cytometry, 5-Ethynyl-2'-deoxyuridine (EdU), CCK-8 and colony formation assays were conducted to evaluate apoptosis and proliferation. The therapeutic efficacy and biosafety of this platform were further validated in a subcutaneous xenograft mouse model. LINC02178 expression was elevated in LUAD tissues and cell lines and correlated with advanced clinical stage and poor prognosis. Gene enrichment analysis indicated that LINC02178 was strongly related to cancer progression and apoptosis. The NPs/2178 platform achieved effective LINC02178 knockdown and demonstrated that the cytotoxicity of LUAD cells was significantly greater than that of mouse fibroblasts. The NPs/2178 gene delivery system significantly promoted LUAD apoptosis and inhibited cell proliferation in vitro. In vivo studies revealed marked tumour growth inhibition by NPs/2178 without observable systemic toxicity. LINC02178 functions as an oncogenic factor that promotes LUAD progression. The NPs/2178 delivery system represents a promising gene therapy strategy.

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