CircPOSTN/miR-361-5p/TPX2 axis regulates cell growth, apoptosis and aerobic glycolysis in glioma cells

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.

Corosolic acid reduces NSCLC cell proliferation, invasion, and chemoresistance via inducing mitochondrial and liposomal oxidative stress

“…TPX2, microtubule-associated protein, regulates the dynamics of mitotic spindles, which is indicative of its important role in the cell cycle [26]. In other studies, TPX2 was demonstrated to function as an oncogene, and TPX2 knockdown promoted apoptosis and blocked tumor cell growth [27].…”

Identification of molecular markers associated with diagnosis and prognosis in lung adenocarcinoma by bioinformatics analysis

“…In ovarian cancer, it can promote the proliferation and migration of human ovarian cancer cells by regulating PLK1 expression [40]. Except for these function, in various cancers can TPX2 also control bladder cancer cell's proliferation and invasion via TPX2-p53-GLIPR1 regulatory circuitry [41], regulate the PI3K/AKT signaling pathway to facilitate hepatocellular carcinoma [42], interactive with miRNA such as miR-485-3p [43], miR-361-5p [44], miR-335-5p [45], miR-216b [46] and so on. Zhou et al have veri ed that TPX2 can activate the epithelial-mesenchymal transition process and promote both the expression and activities of matrix metalloproteinase (MMP)2 and MMP9 in non-small cell lung cancer (NSCLC), which means TPX2 promotes the metastasis and malignant progression of NSCLC and could thus serve as a marker of poor prognosis in NSCLC [47].…”

Circular RNAs in the Central Nervous System

“…Circ-FBXW7 has a tumor suppressor effect in glioma cells by encoding a novel protein and is positively correlated with the overall survival rate ( Yang et al, 2018 ). A recent study found that, apart from regulating cell growth and apoptosis, circ POSTN participated in aerobic glycolysis in glioma via the miR-361-5p/TPX2 axis ( Long et al, 2020 ). Additionally, a recent review reported that most circRNAs function as miRNA sponges in glioma ( Sun et al, 2020 ).…”