No abstract

Background: Glioma is the most primary central nervous system tumor in adults. The 5 year survival rate for glioma patients remains poor, although treatment strategies had improved in the past few decades. The cumulative studies have shown that circular RNA (circRNA) is associated with glioma process, so the purpose of this study is to clarify the function of circPOSTN in glioma. Methods: The expression levels of circPOSTN, miR-361-5p, and targeting protein for Xenopus kinesin-like protein 2 (TPX2) were assessed with real-time quantitative polymerase chain reaction (RT-qPCR). The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were executed to examine proliferation and apoptosis of glioma cells, respectively. Western blot was applied to assess protein expression. The glucose metabolism of glioma cells was analyzed by testing the glucose consumption, lactate production, ATP level, reactive oxygen species (ROS) accumulation and performing Seahorse XF assay. The interaction relationship between miR-361-5p and circPOSTN or TPX2 was analyzed by bioinformatics database and dual-luciferase reporter assay. The influences of circPOSTN silencing in vivo were observed by a xenograft experiment. Results: CircPOSTN was overexpressed in glioma tissues and cells. Absence of circPOSTN in glioma cells promoted apoptosis while impeded proliferation and aerobic glycolysis, which were mitigated by silencing miR-361-5p. What's more, loss-of-functional experiment suggested that knockdown of TPX2 repressed proliferation and aerobic glycolysis, while induced apoptosis in glioma cells. In addition, circPOSTN targetedly regulated TPX2 expression in glioma cells via sponging miR-361-5p. In vivo study revealed that deficiency of circPOSTN restrained tumor growth. Conclusion: Mechanistically, circPOSTN regulated cell growth, apoptosis, and aerobic glycolysis in glioma through miR-361-5p/TPX2 axis.

To detect the aberrantly expressed long non-coding RNAs in glioblastoma, two pairs of glioblastoma and adjacent normal tissues were firstly analyzed by RNA sequencing. Long intergenic non-coding RNA LINC00657 was considered to play a vital role in glioblastoma based on the results of RNA sequencing. Hence, we aimed to investigate the mechanisms by which LINC00657 regulated the tumorigenesis of glioblastoma. The level of LINC00657 in 40 glioblastoma samples and glioblastoma cell lines was detected by RT-qPCR. LINC00657 was significantly decreased in patients with glioblastoma compared with adjacent normal tissues. Overexpression of LINC00657 inhibited proliferation, colony formation, invasion and migration in glioma cells via inducing apoptosis. Dual luciferase report assay indicated LINC00657 was the target of miR-190a-3p. Overexpression of LINC00657 greatly inhibited the relative amount of miR-190a-3p. Besides, miR-190a-3p was found to be a negative regulator of PTEN. Additionally, active-caspase 3 was increased in cells transfected with pcDNA3.1-LINC00657. Finally, in vitro results were further confirmed by in vivo studies using nude mice bearing with glioblastoma tumors. In conclusion, LINC00657 was effective in inhibiting glioblastoma by acting as a molecular sponge of miR-190a-3p to regulate PTEN expression. Therefore, targeting LINC00657 may serve as a potential strategy for the treatment of patients with glioblastoma.