Identification of CD24 as a potential diagnostic and therapeutic target for malignant pleural mesothelioma.
Sivasundaram KarnanAkinobu OtaHideki MurakamiMd Lutfur RahmanMuhammad Nazmul HasanMd WahiduzzamanIchiro HanamuraLam Quang VuAkihito InokoToshinori HyodoHiroyuki KonishiShinobu TsuzukiYoshitaka HosokawaPublished in: Cell death discovery (2020)
Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleura that is currently incurable due to the lack of an effective early diagnostic method and specific medication. The CDKN2A (p16) and NF2 genes are both frequently mutated in MPM. To understand how these mutations contribute to MPM tumor growth, we generated NF2/p16 double-knockout (DKO) cell clones using human MeT-5A and HOMC-B1 mesothelial cell lines. Cell growth and migration activities were significantly increased in DKO compared with parental cells. cDNA microarray analysis revealed differences in global gene expression profiles between DKO and parental cells. Quantitative PCR and western blot analyses showed upregulation of CD24 concomitant with increased phosphorylation of AKT, p70S6K, and c-Jun in DKO clones. This upregulation was abrogated by exogenous expression of NF2 and p16. CD24 knockdown in DKO cells significantly decreased TGF-β1 expression and increased expression of E-cadherin, an epithelial-mesenchymal transition marker. CD24 was highly expressed in human mesothelioma tissues (28/45 cases, 62%) and associated with the loss of NF2 and p16. Public data analysis revealed a significantly shorter survival time in MPM patients with high CD24 gene expression levels. These results strongly indicate the potential use of CD24 as a prognostic marker as well as a novel diagnostic and therapeutic target for MPM.
Keyphrases
- signaling pathway
- induced apoptosis
- poor prognosis
- gene expression
- epithelial mesenchymal transition
- pi k akt
- endothelial cells
- oxidative stress
- nk cells
- cell proliferation
- single cell
- healthcare
- nuclear factor
- endoplasmic reticulum stress
- transforming growth factor
- stem cells
- dna methylation
- mental health
- emergency department
- high resolution
- bone marrow
- immune response
- tyrosine kinase
- risk assessment
- genome wide identification
- adverse drug
- climate change
- bioinformatics analysis
- genome wide analysis
- protein kinase