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Long non-coding RNA GEHT1 promoted the proliferation of ovarian cancer cells via modulating the protein stability of HIF1α

机译:长非编码RNA GEHT1通过调节HIF1α的蛋白质稳定性来促进卵巢癌细胞的增殖

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摘要

Cancer cells preferentially metabolize glucose via the aerobic glycolysis pathway, which is also named as Warburg effect. Increasing evidence has suggested that suppression of glycolysis inhibits the progression of cancers. In the present study, we found that the long non-coding RNA gastric carcinoma high expressed transcript 1 (GHET1) was overexpressed in ovarian cancer tissues and cell lines. Up-regulation of GHET1 was positively correlated with the tumor size and metastasis of the ovarian cancer patients. Overexpression of GEHT1 significantly promoted the proliferation and colony formation of ovarian cancer cells. Mechanistically, the candidate binding partners of GHET1 were explored by pull-down and mass spectrum. Of note, GHET1 was found to interact with the E3 ubiquitin ligase von Hippel-Lindau (VHL), which consequently blocked VHL-mediated degradation of hypoxia-inducible factor-1α (HIF1α) and enhanced the protein level of HIF1α in ovarian cancer cells. The up-regulated HIF1α promoted the glucose uptake and lactate generation of ovarian cancer cells. Collectively, our results suggested the oncogenic function of GHET1 via up-regulating the glycolysis in ovarian cancer and can be considered as a promising anti-cancer target.
机译:癌细胞优先通过有氧糖酵解途径代谢葡萄糖,这也被称为Warburg效应。越来越多的证据表明,抑制糖酵解会抑制癌症的进展。在本研究中,我们发现长期非编码RNA胃癌高表达转录本1(GHET1)在卵巢癌组织和细胞系中过表达。 GHET1的上调与卵巢癌患者的肿瘤大小和转移呈正相关。 GEHT1的过表达显着促进卵巢癌细胞的增殖和集落形成。从机制上讲,通过下拉和质谱分析了GHET1的候选结合伴侣。值得注意的是,发现GHET1与E3泛素连接酶von Hippel-Lindau(VHL)相互作用,从而阻止了VHL介导的缺氧诱导因子1α(HIF1α)降解并增强了卵巢癌细胞中HIF1α的蛋白水平。上调的HIF1α促进卵巢癌细胞的葡萄糖摄取和乳酸生成。总体而言,我们的研究结果表明,通过上调卵巢癌中的糖酵解作用,GHET1的致癌作用可被视为有希望的抗癌靶标。

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