Novel sphingomyelin biomarkers for brain glioma and associated regulation research on the PI3K/Akt signaling pathway

Abstract

Glioma is one of the most common malignant tumor types of the central nervous system. It is necessary to identify biomarkers and novel therapeutic targets for glioma. The purpose of the present study was to distinguish lipid biomarkers with differential expression patterns in glioma tissues and normal brain tissues by matrix assisted laser desorption/ionization (MALDI)-imaging and MALDI-time of flight (TOF)-mass spectrometry (MS). Additionally, identification of lipid biomarkers was performed to describe novel therapeutic targets for glioma treatment. A total of six tissues from three patients with glioma and three control patients with traumatic brain injury were analyzed using UltrafleXtreme MALDI-TOF/TOF. The expression levels of 15 lipid peaks were higher in the TBT samples compared with in the GBT samples. The expression levels of another 16 lipid peaks were higher in the GBT samples compared with in the TBT samples. 14 peaks were identified as sphingomyelins using MS/MS. Additional results were also obtained from experiments using the glioma cell line U373-MG. These results indicated that treatment with the drug desipramine (Desi) inhibited the accumulation of ceramide on the cell membranes of glioma U373-MG cells. Treatment with Desi inhibited the activation of insulin-like growth factor-1 receptor and inhibited the activation of proteins in the PI3K/Akt signaling pathway.

A mass spectrometry imaging and lipidomic investigation reveals aberrant lipid metabolism in the orthotopic mouse glioma

“…Indeed, the interrogation of human glioma gene expression indicated upregulation of SM phosphodiesterase 2, N-acylsphingosine amidohydrolase 1, and sphingosine kinase 1, supporting the above protective mechanism to ensure the tumor cell survival. The observed paradoxical increase of tumoral Cer d18:1/16:0 was also similarly reported in the head and neck squamous cell carcinoma ( 62 ), breast cancer ( 63 ), and glioblastoma ( 64 ). The parallel increase of tumoral SM d18:1/16:0 implied the adaptation of yet another SL metabolic mechanism by the tumoral cells to evade the Cer-mediated apoptosis through the formation of the analogous SM species to promote the proliferation, invasion, and immune evasion of the tumor cells ( 65 ).…”

Diagnosis and Management of Glioblastoma: A Comprehensive Perspective

“…Transcriptomics and other omics technics proposed prognostic tools for the comprehension of the disease [ 81 , 82 ]. Along with these techniques, liquid chromatography and mass spectrometry analyses from different samples such as CSF (Cerebrospinal fluid), urine, blood or glioblastoma cell lines [ 83 ] have provided a comprehensive view of the altered metabolic pathways in patients with glioblastoma [ 84 , 85 ]. More recently, special attention has been given to alterations of lipid metabolism in glioblastomas.…”

RFX1: a promising therapeutic arsenal against cancer

“…RFX1 itself is a relevant tumor suppressor transcription factor in glioblastoma due to its negative regulation of CD44 expression [ 2 ]. On the contrary, weighted gene co-expression network analysis (WGCNA) of lung adenocarcinoma samples designated RFX1 as an enriched transcription factor in microtubule processing and tumor development, which needs further validation [ 58 ]. Recently, a dysregulated network of triplet molecules, including RFX1, TP73-AS1 lncRNA, and miR-197, was perceived to indicate a poor prognosis, survival, and tumor progression in glioblastoma multiforme [ 4 ].…”

“…The aforementioned WGCNA analysis also reported RFX1 as the target of miR-184, a miRNA that is differentially expressed in lung adenocarcinoma [ 58 ]. Previous studies indicated that miR-184 was down-regulated in nasopharyngeal carcinoma and could act as a tumor suppressor [ 92 ] while being upregulated in multiple HCC cell lines like Hep3B, BEL-7402, MHCC97H, HCCC-9810, MHCC97L, and Huh7 [ 93 , 94 ].…”