Exploring the lncRNA NEAT1/iASPP Pathway in Chordoma: Mechanisms of Proliferation Suppression and Apoptosis Induction

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Background: Chordoma is a rare, primary malignant bone tumor arising from remnants of embryonic notochord tissue. While the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has been implicated in various cancers, its role in chordoma remains to be elucidated. This study aims to elucidate the mechanisms by which lncRNA NEAT1 influences chordoma growth and apoptosis. Method: lncRNA NEAT1 expression was assessed in chordoma using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Two chordoma cell lines with high lncRNA NEAT1 expression were selected for lncRNA NEAT1 knockdown and inhibitor of apoptosis-stimulating protein of p53 (iASPP) overexpression experiments. Cell survival was assessed using Cell Counting Kit-8 (CCK-8) and colony formation assays, while apoptosis and iASPP expression levels were analyzed by flow cytometry, Western blotting (WB), and RT-qPCR. In vivo, treated U-CH1 cell lines were subcutaneously injected into nude mice to establish a chordoma model. Tumor apoptosis was evaluated through hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and WB was used to measure the levels of apoptosis-related proteins and iASPP in the tissues. Results: The lncRNA NEAT1 was highly expressed in chordoma. Silencing lncRNA NEAT1 inhibited the survival and proliferation of chordoma cell lines MUG-Chor1 and U-CH1, and promoted apoptosis (p < 0.05). Overexpression of iASPP counteracted these effects, enhanced cell growth and inhibited apoptosis in the si-lncRNA NEAT1 group (p < 0.05). HE and TUNEL staining results indicated that silencing lncRNA NEAT1 reduced cell proliferation and division in chordoma tissues, and led to a marked increase in apoptosis (p < 0.05). These effects were reversed by overexpression of iASPP (p < 0.05). Conclusion: In chordoma, lncRNA NEAT1 is highly expressed, and silencing lncRNA NEAT1 inhibits the proliferation and induces apoptosis of chordoma cells while decreasing the expression of iASPP. These findings offer new insights into the involvement of the lncRNA NEAT1/iASPP pathway in chordoma development.

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