CircVMP1 promotes glycolysis and disease progression by upregulating HKDC1 in colorectal cancer

糖酵解 结直肠癌 癌症研究 下调和上调 细胞生长 己糖激酶 转移 生物 体内 癌症 氧化磷酸化 化学 细胞生物学 生物化学 新陈代谢 基因 遗传学
作者
Hongyu Chen,Xiangnan Li,Lei Yang,Chunxiang Ye,Zhilei Chen,Zhenjun Wang
出处
期刊:Environmental Toxicology [Wiley]
标识
DOI:10.1002/tox.24061
摘要

Circular RNAs (circRNAs) have been reported to play important roles in cancers. Here, we characterized circVMP1 (hsa_circ_0006508), an important circRNA which promoted glycolysis and disease progression in colorectal cancer (CRC). In this study, we aimed to explore the mechanism by which circVMP1 regulated tumor glycolysis and its related pathways in promoting CRC cell proliferation and metastasis.The expression level of circVMP1 in CRC tissues and adjacent normal tissues was detected using quantitative PCR. In vitro and in vivo functional experiments were used to evaluate the effects of circVMP1 in the regulation of CRC cell proliferation and migration. Mitochondrial stress tests and glycolysis stress tests were conducted to detect the effect of circVMP1 on oxidative phosphorylation and glycolysis. Dual-luciferase reporter and RNA immunoprecipitation assays were used to evaluate the interaction between circVMP1, miR-3167, and HKDC1.We demonstrated that the level of circVMP1 was significantly upregulated in CRC tissues compared with normal tissues. In HCT116 and SW480 cells, overexpression of circVMP1 promoted proliferation, metastasis, and glycolysis. In vivo analysis indicated that circVMP1 accelerated the proliferation of xenograft tumors. As for the mechanism, overexpression of circVMP1 increased the levels of hexokinase domain component 1 (HKDC1) through competitive binding with miR-3167.Our study reported that circVMP1 was one of the tumor driver genes that promoted CRC malignant progression and glycolysis by upregulating HKDC1. CircVMP1/miR-3167/HKDC1 was a signaling axis that might be a target for CRC therapy.
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