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

• Published in: Environmental toxicology 2024-03, Vol.39 (3), p.1617-1630
• Main Authors: Chen, Hong‐Yu, Li, Xiang‐Nan, Yang, Lei, Ye, Chun‐Xiang, Chen, Zhi‐Lei, Wang, Zhen‐Jun
• Format: Article
• Language: English
• Subjects: Cancer; Cell growth; Cell migration; Cell proliferation; circRNA; Circular RNA; Colorectal cancer; Colorectal carcinoma; Genes; Glycolysis; Hexokinase; HKDC1; hsa_circ_0006508; Immunoprecipitation; In vivo methods and tests; Metastases; Metastasis; Neoplasms; Nucleotide sequence; Oxidative phosphorylation; PCR; Phosphorylation; Proliferation; Tissue; Tumors; Xenotransplantation
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.24061

Background 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. Methods 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. Results 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. Conclusion 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.