Abstract
BackgroundGlioma is the most common central nervous system (CNS) tumour. p62, an important autophagy adaptor, plays a crucial role in cancer. However, the role of p62 in the progression of glioma is poorly characterized.MethodsWe examined the expression of p62 in glioma tissues and cell lines. Then we investigated the function of p62 in vitro, and clarified the mechanism underlying the regulation of p62 expression.ResultsWe revealed that p62 was upregulated at both the mRNA and protein levels in human glioma tissues irrelevant to isocitrate dehydrogenase (IDH) status. Then, we found that overexpression of p62 promoted glioma progression by promoting proliferation, migration, glycolysis, temozolomide (TMZ) resistance and nuclear factor κB (NF-κB) signalling pathway, and repressing autophagic flux and reactive oxygen species (ROS) in vitro. In accordance with p62 overexpression, knockdown of p62 exerted anti-tumour effects in glioma cells. Subsequently, we demonstrated that miR-124-3p directly targeted the 3′-UTR of p62 mRNA, leading to the downregulation of p62. Finally, we found that p62 function could be partially reversed by miR-124-3p overexpression.ConclusionsOur results demonstrate that p62 can be targeted by miR-124-3p and acts as an oncogene in glioma, suggesting the potential value of p62 as a novel therapeutic target for glioma.
Highlights
Glioma is the most common central nervous system (CNS) tumour. p62, an important autophagy adaptor, plays a crucial role in cancer
The mutant firefly luciferase reporter plasmids, had no effect on luciferase activity in either the pre-miR124-3p or pre-ncRNA groups. These results indicate that the p62 mRNA 3′-untranslated region (3′-UTR) is directly targeted by miR124-3p, leading to the downregulation of p62 expression at both the mRNA and protein levels
We focused on the functions of p62 and demonstrated that the accumulation of p62 could promote glioma by regulating autophagy, proliferation, migration, reactive oxygen species, TMZ resistance, glycolysis and nuclear factor κB (NF-κB) signalling pathway
Summary
Glioma is the most common central nervous system (CNS) tumour. p62, an important autophagy adaptor, plays a crucial role in cancer. Glioma is the most common central nervous system (CNS) tumour. P62, an important autophagy adaptor, plays a crucial role in cancer. Malignant gliomas (grade III to IV), which are associated with a dismal prognosis, constitute the p62, encoded by SQSTM1, is the most well-known autophagy adaptor, and it plays a crucial role in both normal physiology and cancer. Research on p62 aberrance in the CNS has mainly focused on neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease, while the role of p62 in the progression of glioma is poorly characterized. MiR124-3p can inhibit glioma progression through repressing proliferation, invasion and the stem-like traits, and potentiating chemosensitivity by targeting different genes [11, 12]. We identified the anti-tumour effect of miR-124-3p in the pathogenesis of astrocytoma by targeting PIM1 [13]
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