MicroRNA-129-5p Regulates Glycolysis and Cell Proliferation by Targeting the Glucose Transporter SLC2A3 in Gastric Cancer Cells.

MicroRNA-129-5p Regulates Glycolysis and Cell Proliferation by Targeting the Glucose Transporter SLC2A3 in Gastric Cancer Cells.
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MicroRNA-129-5p 通过靶向胃癌细胞中的葡萄糖转运蛋白 SLC2A3 来调节糖酵解和细胞增殖

DOI:
10.3389/fphar.2018.00502
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发表时间:
2018
影响因子:
5.6
通讯作者:
He X
He X
中科院分区:
医学2区
文献类型:
--
作者:
Chen D;Wang H;Chen J;Li Z;Li S;Hu Z;Huang S;Zhao Y;He X

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肿瘤细胞通过有氧糖酵解增加葡萄糖消耗,以制造增殖所需的必要生物量,这通常被称为Warburg效应。越来越多的证据表明,microRNAs (miRNAs)与其靶基因相互作用,有助于癌细胞的代谢重编程。通过整合高通量筛选数据和现有的miRNA表达数据集,我们探索了候选糖代谢调节miRNA在胃癌(GC)中的作用。随后对表征的mirna的研究表明,miR-129-5p抑制GC细胞的葡萄糖代谢。miRNA-129-5p直接靶向SLC2A3的3 ' -UTR,从而抑制GC细胞的葡萄糖消耗、乳酸生成、细胞ATP水平和葡萄糖摄取。此外,PI3K-Akt和MAPK信号通路参与miR-129-5p/SLC2A3轴的作用,调节GC糖代谢和生长。这些结果揭示了miR-129-5p/SLC2A3轴在GC细胞糖代谢过程重编程中的新作用,并指出了治疗这种疾病的潜在治疗靶点。
Tumor cells increase their glucose consumption through aerobic glycolysis to manufacture the necessary biomass required for proliferation, commonly known as the Warburg effect. Accumulating evidences suggest that microRNAs (miRNAs) interact with their target genes and contribute to metabolic reprogramming in cancer cells. By integrating high-throughput screening data and the existing miRNA expression datasets, we explored the roles of candidate glycometabolism-regulating miRNAs in gastric cancer (GC). Subsequent investigation of the characterized miRNAs indicated that miR-129-5p inhibits glucose metabolism in GC cells. miRNA-129-5p directly targets the 3′-UTR of SLC2A3, thereby suppressing glucose consumption, lactate production, cellular ATP levels, and glucose uptake of GC cells. In addition, the PI3K-Akt and MAPK signaling pathways are involved in the effects of the miR-129-5p/SLC2A3 axis, regulating GC glucose metabolism and growth. These results reveal a novel role of the miR-129-5p/SLC2A3 axis in reprogramming the glycometabolism process in GC cells and indicate a potential therapeutic target for the treatment of this disease.
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