Abstract
Glioma is a prevalent brain malignancy with aggressive progression and with grave prognosis in adults. Circular RNAs have been reported to regulate glioma development and function as the diagnostic, prognostic, and therapeutic biomarkers. In this study, we were interested the function of circular RNA ZNF609 in modulating glioma. Remarkably, knockdown of ZNF609 by siRNA in glioma cells reduced cell viabilities and Edu-positive. The silencing of ZNF609 stimulated the apoptosis of glioma cells. Meanwhile, the ZNF609 depletion inhibited the invasion and migration of glioma cells. In glioma cells, the mRNA and protein expression of E-cadherin was enhanced, while Vimentin was reduced by the inhibition of ZNF609. The glucose uptake, lactate product, and ATP production in glioma cells were suppressed by ZNF609 knockdown. Mechanically, miR-378b was sponged by ZNF609 and targeted SLC2A1 in glioma cells. ZNF609 enhanced SLC2A1 expression by inhibiting miR-378b. The inhibition of miR-378b or the enhancement of SLC2A1 reversed ZNF609 depletion-regulated glioma cell proliferation in vitro. The depletion of ZNF609 suppressed glioma cell growth in the nude mice. Therefore, we concluded that ZNF609 contributed to cell survival and glycolysis of glioma by targeting miR-378b/SLC2A1 axis. ZNF609 and miR-378b may function as potential treatment targets in glioma.
Highlights
Glioma is regarded as the most frequently occurring malignancy among brain tumors in adults, which is highly aggressive and with grave prognosis [1]
Given that SLC2A1 is a critical factor in the regulation of glycolysis, we explored the effect of circZNF609 on SLC2A1 and the potential interaction of miR-378b with circZNF609 and SLC2A1 was screened by the bioinformatics analysis in the ENCORI database from several potential miRNAs
ZNF609 contributes to proliferation of lung cancer cells by regulating miR1224-3p/ETV1 axis [27]
Summary
Glioma is regarded as the most frequently occurring malignancy among brain tumors in adults, which is highly aggressive and with grave prognosis [1]. Cancer development is a complicated process result from various aspects regarding proliferation, apoptosis, angiogenesis, and especially metabolism [2]. The importance of metabolism has caused great attention in the cancer research area, due to the essential role of energy supplements in the maintenance of cell vitality [3]. Among the metabolism manners, enhanced glycolysis is proposed as an essential process for the initiation and development of cancer [4]. It is well accepted that aerobic glycolysis is the major metabolic type in cancer cells, rather than the common oxidative phosphorylation in normal cells, even with the existence of oxygen, and this phenomenon is named the Warburg effect [5]. As a highly metastatic cancer type, glioma is reported to be associated with glycolysis, involving the proliferation, inflammation, migration, and immune response [10]
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