hsa-let-7b-5p/TMPO-AS1-mediated ceRNA networks are linked to poor prognosis for lung cancer patients with FOXM1/MAD2L1 axis.

objectivesMAD2L1, a spindle assembly checkpoint molecule, is associated in cancer cell proliferation and carcinogenesis, although its ceRNA network is unknown.

methodsInitially, patient's survivability associated with the gene expression was analysed by using the Kaplan-Meier plotter database. Here, we used several TCGA databases such as UALCAN, OncoDB, ENCORI, lung cancer explorer, GEPIA2, TCGAnalyzer, and CancerMIRNome to identify differential mRNA, miRNA, and lncRNA expression. The Enrichr database was utilized to identify the transcription factor regulating MAD2L1, which was then correlated with miRNA and lncRNA, forming the ceRNA network using the miRNet database. Database miRWalk and RNA22v2 were used to predict the folding energy and binding affinity between the MAD2L1 and miRNA. TIMER and TIMER 2.0 databases were incorporated to analyse the tumor infiltrating immune cells in LUAD.

resultsThe study found that overexpression of MAD2L1 in lung cancer patients is a high-risk factor for lung adenocarcinoma (LUAD) (HR = 1.34, P = 0.001), particularly in smoker females (HR = 1.61, P = 0.018). The study revealed MAD2L1 overexpression in LUAD cases, with a fold change of 8.7, and a strong positive correlation between RNA and protein expression levels by Cancer Proteome (R = 0.764). The study identified regulatory molecules of MAD2L1 such as transcription factor FOXM1 (R = 0.770), and lncRNA TMPO-AS1 (R = 0.565) as positively correlated with MAD2L1, while miRNA hsa-let-7b-5p, negatively correlated with MAD2L1 (R = - 0.314), FOXM1 (R = - 0.393), and TMPO-AS1 (R = - 0.277). The study suggests that TMPO-AS1 suppresses tumor suppression activity of let-7b-5p and targeting hsa-let-7b-5p could regulate MAD2L1, FOXM1 and lncRNA expression levels in LUAD. Additionally, a strong folding and binding energy was identified between the MAD2L1 gene and hsa-let-7b-5p. After analyzing the tumor microenvironment, we found that CD4+ T cells and B cells negatively correlate with the overexpression of MAD2L1.

conclusionThe study indicates that MAD2L1 is overexpressed in females with LUAD, highlighting its potential as a molecular classifier and prognostic biomarker, and introduces a novel regulatory ceRNA network.