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首页> 外文期刊>Journal of Cellular Physiology >Triose-phosphate isomerase is a novel target of miR-22 and miR-28, with implications in tumorigenesis
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Triose-phosphate isomerase is a novel target of miR-22 and miR-28, with implications in tumorigenesis

机译：磷酸丙糖异构酶是一种新型的目标miR-22 miR-28,影响肿瘤发生

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摘要

Aerobic glycolysis is the hallmark of many cancer cells that results in a high rate of adenosine triphosphate (ATP) production and, more importantly, biosynthetic intermediates, which are required by the fast-growing tumor cells. The molecular mechanism responsible for the increased glycolytic influx of tumor cells is still not fully understood. In the present study, we have attempted to address the above question by exploring the role of the glycolytic enzyme, triose-phosphate isomerase (TPI), in the cancer cells. The western blot analysis of the 30 human colorectal cancer samples depicted higher post-transcriptional expression of TPI in the tumor tissue relative to the normal tissue. In addition, we identified two novel microRNAs, miR-22 and miR-28, that target the TPI messenger RNA (mRNA) and regulate its expression. miR-22 and the miR-28 showed significant inverse expression status viz-a-viz the expression of the TPI. The specificity of the miR-22/28 regulation of the TPI mRNA was confirmed by various biochemical and mutagenic assays. Moreover, the hypoxia conditions resulted in an increased expression of the TPI protein, with a concomitant decrease in miR-22/28. The physiological significance of the TPI and miR-22/28 interaction for the glycolytic influx was confirmed by the l-lactate production in the HCT-116(+/+) cells. Overall, our data demonstrate the novel microRNA mediated post-transcriptional regulation of the TPI glycolytic enzyme, which may be one of the possible reasons for the increased glycolytic capacity of the tumor cells.
机译：有氧糖酵解是许多癌症的标志细胞,导致高速率的腺苷三磷酸腺苷(ATP)生产,更多重要的是,生物合成的中间体,需要快速增长的肿瘤细胞。负责增加的分子机制糖酵解的肿瘤细胞仍没有完全理解。试图解决上述问题探索糖酵解酶的作用,磷酸丙糖异构酶(TPI)的癌症细胞。结直肠癌标本描述更高转录后TPI的表达式肿瘤组织与正常组织。此外,我们发现两个新型小分子核糖核酸,miR-22 miR-28,目标TPI信使核糖核酸(mRNA)及调控其表达。miR-28显示明显的逆viz-a-viz表达状态的表达TPI。证实了TPI mRNA的不同生化和诱变化验。缺氧条件下导致了增加TPI的表达蛋白质,相伴miR-22/28下降。TPI的意义和miR-22/28交互证实了糖酵解涌入l-lactate生产hct - 116(+ / +)细胞。总的来说,我们的数据展示小说微rna介导的转录后调控的TPI糖酵解酶,这可能是其中的一个可能的原因为糖酵解增加肿瘤细胞的能力。

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