Long non-coding RNA LINC00470 in serum derived exosome: a critical regulator for proliferation and autophagy in glioma cells

• Published in: Cancer cell international Vol. 21; no. 1; p. 149
• Main Authors: Ma, Wenjia, Zhou, Yu, Liu, Min, Qin, Qilin, Cui, Yan
• Format: Journal Article
• Language: English
• Published: England BioMed Central 04.03.2021; BMC
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antibodies; Apoptosis; Autophagy; Brain cancer; Cancer therapies; Cell proliferation; Exosome; Exosomes; Flow cytometry; Glioma; Glioma cells; Immunoprecipitation; Kinases; Laboratory animals; LINC00470; Medical prognosis; MicroRNAs; miR-580-3p; Mitochondrial DNA; Non-coding RNA; Phagocytosis; PI3K/AKT/mTOR; Primary Research; TOR protein; Tumors; WEE1; United States > US; Germany; WEE1; PI3K/AKT/mTOR; Glioma; Exosome; LINC00470; Proliferation; Autophagy; miR-580-3p
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-021-01825-y

To explore the mechanism of LINC00470 in serum exosomes from glioma patients regulating the autophagy and proliferation of glioma cells. Exosomes were extracted from glioma patients (GBM-exo). Expression of LINC00470 in exosomes was analyzed with the clinicopathological characteristics of glioma patients. Glioma mouse model was established. The effects of LINC00470, miR-580-3p and WEE1 on cell autophagy and proliferation, as well as the activation of PI3K/AKT/mTOR pathway were measured. Dual luciferase reporter assay and RNA immunoprecipitation (RIP) were conducted to validate the binding of LINC00470 and miR-580-3p and of miR-580-3p and WEE1. LINC00470 overexpressed in GBM-exo and associated with disease severity and postoperative survival time of glioma patients. GBM-exo deteriorated tumor progression in nude mice. Cells incubated with GBM-exo or transfected with pcDNA3.1-LINC00470/miR-580-3p inhibitor/pcDNA3.1-WEE1 had less autophagosome, downregulated LC3-II/LC3-I and Beclin1 expression levels and increased expression of p62 as well as strengthened proliferation ability. The PI3K/AKT/mTOR pathway was activated. LINC00470 competitively bound to miR-580-3p with WEE1. LINC00470 in GBM-exo can bind to miR-580-3p in glioma cells to regulate WEE1 expression and activate the PI3K/AKT/mTOR pathway, thereby inhibiting autophagy and enhancing the proliferation of glioma cells.