RESUMEN
INTRODUCTION: Peritumoral brain edema (PTBE) has been widely reported with many brain tumors, especially with glioma. Since the blood-brain barrier (BBB) is essential for maintaining minimal permeability, any alteration in the interaction of BBB components, specifically in astrocytes and tight junctions (TJ), can result in disrupting the homeostasis of the BBB and making it severely leaky, which subsequently generates edema. OBJECTIVE: This study aimed to evaluate the functional gliovascular unit of the BBB by examining changes in the expression of claudin (CLDN) genes and the expression of transient receptor potential (TRP) membrane channels, additionally to define the correlation between their expressions. The evaluation was conducted using in vitro spheroid swelling models and tumor samples from glioma patients with PTBE. RESULTS: The results of the spheroid model showed that the genes TRPC3, TRPC4, TRPC5, and TRPV1 were upregulated in glioma cells either wild-type isocitrate dehydrogenase 1 (IDH1) or the IDH1 R132H mutant, with or without NaCl treatment. Furthermore, TRP genes appeared to adversely correlate with the up regulation of CLDN1, CLDN3, and CLDN5 genes. Besides, the upregulation of TRPC1 and TRPC4 in IDH1mt-R132H glioma cells. On the other hand, the correlation analysis revealed different correlations between different proteins in PTBE. CLDN1 exhibits a slight positive correlation with CLDN3. Similarly, TRPV1 displays a slight positive correlation with TRPC1. In contrast, TRPC4 shows a slight negative correlation with TRPC5. On the other hand, TRPC3 demonstrates a slight positive correlation with TRPC5, while the non-PTBE analysis highlights a moderate positive correlation between CLDN1 and TRPM4 while CLDN3 exhibits a moderate negative correlation with TRPC4. Additionally, CLDN5 demonstrates a slight negative correlation with TRPC4 but a moderate positive correlation with TRPC3. Furthermore, TRPC1 have a slight negative correlation with TRPV1, TRPC3 exhibiting a slight positive correlation with TRPC4, and TRPV1 showing a slight negative correlation with TRPC5. CONCLUSION: As a conclusion, the current study provided evidence of a slight negative correlation between TRPs and CLDN gene expression in PTBE patients and confirmatory results with some of the genes in cell model of edema.
Asunto(s)
Edema Encefálico , Neoplasias Encefálicas , Claudina-5 , Glioma , Humanos , Edema Encefálico/genética , Edema Encefálico/metabolismo , Edema Encefálico/patología , Glioma/genética , Glioma/metabolismo , Glioma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Claudina-5/genética , Claudina-5/metabolismo , Regulación Neoplásica de la Expresión Génica , Claudina-3/genética , Claudina-3/metabolismo , Barrera Hematoencefálica/metabolismo , Canales Catiónicos TRPC/genética , Canales Catiónicos TRPC/metabolismo , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Línea Celular Tumoral , Claudina-1/genética , Claudina-1/metabolismo , Claudinas/genética , Claudinas/metabolismo , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo , MasculinoRESUMEN
The emergence of RNA modifications has recently been considered as critical post-transcriptional regulations which governed gene expression. N6-methyladenosine (m6A) modification is the most abundant type of RNA modification which is mediated by three distinct classes of proteins called m6A writers, readers, and erasers. Accumulating evidence has been made in understanding the role of m6A modification of non-coding RNAs (ncRNAs) in cancer. Importantly, aberrant expression of ncRNAs and m6A regulators has been elucidated in various cancers. As the key role of ncRNAs in regulation of cancer hallmarks is well accepted now, it could be accepted that m6A modification of ncRNAs could affect cancer progression. The present review intended to discuss the latest knowledge and importance of m6A epigenetic regulation of ncRNAs including mircoRNAs, long non-coding RNAs, and circular RNAs, and their interaction in the context of cancer. Moreover, the current insight into the underlying mechanisms of therapy resistance and also immune response and escape mediated by m6A regulators and ncRNAs are discussed.