lncRNA MALAT1调控GPx3去甲基化参与非小细胞肺癌的发生发展

lncRNA MALAT1 Regulates GPx3 Demethylation and is Involved in the Occurrence and Development of Non-Small Cell Lung Cancer

目的探讨长链非编码RNA(lncRNA)MALAT1通过调控谷胱甘肽过氧化物酶3(GPx3)对非小细胞肺癌(NSCLC)增殖与侵袭的影响及其机制。方法通过TCGA数据库分析NSCLC患者的mRNA表达信息、甲基化数据及其临床信息,确定关键基因MALAT1与GPx3在NSCLC中的表达差异及其与患者预后之间的关系。采用免疫组织化学染色评估GPx3在肺腺癌组织中的表达水平,通过细胞培养、实时定量PCR、MTT法检测细胞增殖、细胞克隆形成以及迁移与侵袭能力来研究抑制MALAT1表达对A549细胞增殖与侵袭能力的影响。蛋白免疫印迹实验用于检测相关蛋白表达的变化。结果在NSCLC组织中,MALAT1的表达显著升高且与患者不良预后相关;GPx3的表达水平则显著降低,GPx3低表达患者的总生存率显著低于高表达组。其中MALAT1高甲基化水平与肺腺癌发生发展关系密切。沉默MALAT1可显著抑制肺癌细胞的增殖、克隆形成以及迁移和侵袭能力,同时促进GPx3的表达。蛋白表达分析进一步证实MALAT1的沉默减少了肿瘤干细胞标志物的表达,并抑制了上皮-间充质转化(EMT)过程。MALAT1通过募集LSD2调控GPx3的表达,从而在NSCLC的发展中发挥关键作用。结论lncRNA MALAT1通过抑制GPx3表达,促进NSCLC肿瘤细胞的增殖与侵袭能力。MALAT1高表达及高甲基化水平与NSCLC患者不良预后之间存在密切关联,为NSCLC的早期诊断、治疗及预后评估提供了新的生物标志物。

Objective Non-small cell lung cancer(NSCLC)is the leading cause of cancer-related death worldwide.This study aimed to investigate the effects of the long noncoding RNA(lncRNA)MALAT1 on the proliferation and invasion of NSCLC through the regulation of glutathione peroxidase 3(GPx3)and its mechanism.Methods By analyzing the mRNA expression information,methylation data,and clinical information of NSCLC patients in the TCGA database,the differences in the expression of the key genes MALAT1 and GPx3 and their relationships with patient prognosis were identified.The expression level of GPx3 in lung adenocarcinoma tissue was evaluated via immunohistochemical staining.Moreover,cell culture,real-time quantitative PCR,MTT assays for cell proliferation,colony formation,and migration and invasion experiments were used to study the effects of inhibiting the lncRNA MALAT1 on the proliferation and invasion of A549 cells.In addition,Western blotting was used to detect changes in related protein expression.Results In NSCLC tissue,MALAT1 expression was significantly increased and associated with poor prognosis,whereas GPx3 expression was significantly decreased,and patients with low GPx3 expression had significantly lower overall survival rates than those with high GPx3 expression.High levels of MALAT1 methylation are closely associated with the occurrence and development of lung adenocarcinoma.Silencing the lncRNA MALAT1 significantly inhibited the proliferation,colony formation ability,migration,and invasion ability of lung cancer cells while promoting the expression of GPx3.Protein level analysis further confirmed that silencing MALAT1 reduced the expression of tumor stem cell markers and inhibited the epithelial-mesenchymal transition(EMT)process.The lncRNA MALAT1 plays a key role in the development of NSCLC by recruiting LSD2 to regulate GPx3 expression.Conclusion The novel mechanism by which the lncRNA MALAT1 promotes tumor cell proliferation and invasion in NSCLC by regulating GPx3 expression provides new biomarkers for the early diagnosis,treatment,and prognostic assessment of NSCLC,highlighting the relationship between the expression levels and methylation levels of MALAT1 and GPx3 and their relationship with the prognosis of NSCLC patients.