MicroRNA-488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3
MicroRNA-488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3
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MicroRNA-488 通过调节 PFKFB3 抑制人前列腺癌细胞的增殖和糖酵解。
DOI：
10.1002/2211-5463.12718
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发表时间：
2019-08-22
期刊：
影响因子：
2.6
通讯作者：
Wen, Xinqiao
中科院分区：
文献类型：
--
作者：
Wang, Jun;Li, Xiaojuan;Wen, Xinqiao
前列腺癌（PCa）仍是美国男性癌症相关死亡的第二大主要原因，其分子机制仍有待阐明。近期研究表明，微小核糖核酸（microRNA）可能在癌症的发生和发展过程中发挥重要作用。通过分析基因表达综合数据库（Gene Expression Omnibus）数据集，我们发现与正常组织相比，前列腺癌组织中miR - 488的表达水平较低。此外，CCK - 8实验、5 - 乙炔基 - 2’ - 脱氧尿苷（EdU）实验、葡萄糖摄取实验以及乳酸分泌实验显示，在前列腺癌细胞系PC3和DU145中过表达miR - 488会抑制细胞增殖和糖酵解。相反，下调miR - 488的表达则会促进前列腺癌细胞的增殖和糖酵解。通过生物信息学方法和双荧光素酶报告基因实验，我们确定6 - 磷酸果糖 - 2 - 激酶/果糖 - 2,6 - 二磷酸酶3型异构体（PFKFB3）是miR - 488的直接作用靶点。抑制PFKFB3也会抑制前列腺癌细胞的糖酵解和增殖。我们的研究表明，miR - 488通过作用于PFKFB3来抑制前列腺癌细胞的增殖和糖酵解，因此，miR - 488可能是前列腺癌一种新的潜在治疗靶点。
Prostate cancer (PCa) remains the second leading cause of cancer-related death among men in the United States, and its molecular mechanism remains to be elucidated. Recent studies have suggested that microRNAs may play an important role in cancer development and progression. By analyzing the Gene Expression Omnibus dataset, we found lower expression for miR-488 in PCa than in normal tissues. Moreover, CCK-8, EdU, glucose uptake, and lactate secrete assays revealed that overexpression of miR-488 in PCa cell lines PC3 and DU145 resulted in inhibition of proliferation and glycolysis. In contrast, downregulation of miR-488 expression promoted proliferation and glycolysis in PCa cells. Using a bioinformatic approach and dual-luciferase reporter assays, we identified 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform3 (PFKFB3), as a direct target of miR-488. Inhibition of PFKFB3 also suppressed PCa cell glycolysis and proliferation. Our study suggests that miR-488 inhibits PCa cell proliferation and glycolysis by targeting PFKFB3, and thus, miR-488 may be a novel therapeutic candidate for PCa.