Abstract
A stem-like subpopulation existed in GBM cells, called glioma stem cells (GSCs), might contribute to cancer invasion, angiogenesis, immune evasion, and therapeutic resistance, providing a rationale to eliminate GSCs population and their supporting niche for successful GBM treatment. LincRNA-p21, a novel regulator of cell proliferation, apoptosis and DNA damage response, is found to be downregulated in several types of tumor. However, little is known about the role of lincRNA-p21 in stemness and radioresistance of GSCs and its regulating mechanisms. In this study, we found that lincRNA-p21 negatively regulated the expression and activity of β-catenin in GSCs. Downregulation of lincRNA-p21 in GSCs was resulted from upregulation of Hu antigen R (HuR) expression caused by miR-146b-5p downregulation. MiR-146b-5p overexpression increased apoptosis and radiosensitivity, decreased cell viability, neurosphere formation capacity and stem cell marker expression, and induced differentiation in GSCs. Moreover, knock-down lincRNA-p21 or HuR and β-catenin overexpression could rescue the phenotypic changes resulted from miR-146b-5p overexpression in GSCs. These findings suggest that targeting the miR-146b-5p/HuR/lincRNA-p21/β-catenin signaling pathway may be valuable therapeutic strategies against glioma.
Highlights
A growing body of evidence suggest that a stemlike subpopulation existed in glioblastoma multiforme (GBM) cells, named glioma stem cells (GSCs), should be responsible for tumor growth, resistance to therapy and recurrence [1,2,3,4]
Downregulation of lincRNA-p21 in GSCs was resulted from upregulation of Hu antigen R (HuR) expression caused by miR-146b-5p downregulation
The results showed that lincRNA-p21 expression in GBM and GSCs cell lines were lower than normal astrocytes cell line NHA
Summary
A growing body of evidence suggest that a stemlike subpopulation existed in glioblastoma multiforme (GBM) cells, named glioma stem cells (GSCs), should be responsible for tumor growth, resistance to therapy and recurrence [1,2,3,4]. GSCs grow like nonadherent spheres in serum-free medium and showed potent tumor formation ability in immuno-compromised mice [7]. They contribute to cancer invasion, angiogenesis, immune evasion, and therapeutic resistance, providing a rationale to eliminate GSCs population and their supporting niche for successful GBM treatment [811]. We know little about the pathological function of lincRNA-p21 in glioma cells and GSCs
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