lncRNA MALAT1 Regulates GPx3 Demethylation and is Involved in the Occurrence and Development of Non-Small Cell Lung Cancer
10.3870/j.issn.1672-0741.24.04.007
- VernacularTitle:lncRNA MALAT1调控GPx3去甲基化参与非小细胞肺癌的发生发展
- Author:
Deguang KONG
1
;
Yan YANG
;
Weiwei YU
Author Information
1. 武汉大学人民医院乳腺甲状腺外科,武汉 430060
- Keywords:
lncRNA MALAT1;
NSCLC;
GPx3;
methylation;
cancer stem cells;
epithelial-mesenchymal transition
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2024;53(5):569-577
- CountryChina
- Language:Chinese
-
Abstract:
Objective Non-small cell lung cancer(NSCLC)is the leading cause of cancer-related death worldwide.This stud-y 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 in-formation,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 quantita-tive 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 expres-sion 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 significant-ly inhibited the proliferation,colony formation ability,migration,and invasion ability of lung cancer cells while promoting the ex-pression 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 de-velopment 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.
