miR-485-5p/NQO1 axis drives colorectal cancer progression by regulating apoptosis and aerobic glycolysis.

IF 5.3 2区 医学 Q1 ONCOLOGY
Yixuan Wang, Houkun Zhou, Ying Liu, Xingyu Zhao, Shuhao Wang, Zhenhua Lin
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引用次数: 0

Abstract

Background: Cancer cells undergo a metabolic shift termed the Warburg effect, transitioning from oxidative phosphorylation to aerobic glycolysis and promoting rapid tumor proliferation. Quinone oxidoreductase (NQO1), a cytosolic flavoprotein, is important for reprogramming cancer cell metabolism. Therefore, NQO1's function in aerobic glycolysis and impact on colorectal cancer (CRC) development and progression was investigated.

Methods: The clinical significance of NQO1 was evaluated by analyzing online databases and was substantiated in CRC specimens. NQO1's influence on proliferation, epithelial-mesenchymal transition (EMT), metastasis, apoptosis, and glycolytic pathways in CRC cells was evaluated using in vitro and in vivo experiments. The molecular interactions between NQO1 and microRNA-485-5p (miR-485-5p) were ascertained via quantitative reverse transcription PCR and dual luciferase reporter assays. The molecular mechanisms underlying the miR-485-5p/NQO1 axis and its effects on progression of malignancy and aerobic glycolysis in CRC cell lines were investigated.

Results: NQO1 promoted CRC cell proliferation and EMT, augmented their metastatic potential, and suppressed their apoptosis. The NQO1 overexpression-mediated enhancement of glycolytic activity is implicated in the increased proliferation, EMT, and metastatic abilities of, and reduced apoptosis in, CRC cells. Further, miR-485-5p may inhibit the proliferative and invasive traits of CRC cells by directly targeting the 3' untranslated region of NQO1 mRNA.

Conclusions: miR-485-5p/NQO1 signaling axis orchestrates aerobic glycolysis, thereby modulating CRC cell proliferation, metastasis, and apoptosis. Our study provides mechanistic perspectives regarding the role of NQO1 in CRC progression.

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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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