Abstract
Glioma is the most common malignancy of the central nervous system. Although advances in surgical resection, adjuvant radiotherapy, and chemotherapy have been achieved in the last decades, the prognosis of gliomas is still dismal. COL5A1 is one of the collagen members with minor content but prominent functions. The present study examined the biological functions, prognostic value, and gene-associated tumor-infiltrating immune cells of COL5A1 through experiments and bioinformatics analysis. We found that the overexpression of COL5A1 was positively correlated with the increasing tumor malignancies and indicated poor prognosis in gliomas. Moreover, downregulation of COL5A1 could inhibit proliferation and migration of glioma cells and enhance their temozolomide sensitivities in vitro. Further bioinformatic analysis revealed that COL5A1 and its co-expressed genes participated in a number of pathways and biological processes involved in glioma progression. Finally, we evaluated the tumor-infiltrating immune cells of gliomas depending on COL5A1 and found that the percentages of the dendritic cells, which were known as the central mediator of tumor microenvironment in gliomas, were positively associated with the expression levels of COL5A1. Taken together, COL5A1 is an important biomarker and potential therapeutic target of gliomas.
Highlights
Glioma is the most common malignancy in the brain, accounting for more than 70% malignancies of the entire central nervous system [1]
Three groups of glioma cells were included in this study, of which the blank group referred to cells not transfected, while the non-specific control (NC) and siCOL5A1 groups represented glioma cells transfected with nonspecific control siRNA and si-COL5A1, respectively
We found that the expression levels of COL5A1 increased along with tumor grades significantly (Figure 1A)
Summary
Glioma is the most common malignancy in the brain, accounting for more than 70% malignancies of the entire central nervous system [1]. Since a majority of low-grade gliomas, during treatment, convert to higher grades or even evolve in secondary GBMs, tumor progression is a thorny problem in the treatment of gliomas. Temozolomide (TMZ) is an oral antitumor drug approved by the US Food and Drug Administration (FDA) for the treatment of Functions of COL5A1 in Gliomas glioma. At least 50% of gliomas do not respond to TMZ, of which some patients are intrinsically positive for resistance-related genes, such as p53 mutation, homeostatic iron regulator (HFE) mutation, and O6-methylguanine-DNA alkyltransferase (MGMT) promoter unmethylation; the others acquire the resistance after TMZ administration [4]. It is crucial to pursuing new targets of gliomas concerning tumor progression and TMZ chemoresistance for improving prognosis of gliomas
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