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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >SRSF3 a Splicer of the PKM Gene Regulates Cell Growth and Maintenance of Cancer-Specific Energy Metabolism in Colon Cancer Cells
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SRSF3 a Splicer of the PKM Gene Regulates Cell Growth and Maintenance of Cancer-Specific Energy Metabolism in Colon Cancer Cells

机译：SRSF3PKM基因的剪接物调节结肠癌细胞中细胞的生长和癌症特异性能量代谢的维持。

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Serine and arginine rich splicing factor 3 (SRSF3), an SR-rich family protein, has an oncogenic function in various kinds of cancer. However, the detailed mechanism of the function had not been previously clarified. Here, we showed that the SRSF3 splicer regulated the expression profile of the pyruvate kinase, which is one of the rate-limiting enzymes in glycolysis. Most cancer cells express pyruvate kinase muscle 2 (PKM2) dominantly to maintain a glycolysis-dominant energy metabolism. Overexpression of SRSF3, as well as that of another splicer, polypyrimidine tract binding protein 1 (PTBP1) and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), in clinical cancer samples supported the notion that these proteins decreased the Pyruvate kinase muscle 1 (PKM1)/PKM2 ratio, which positively contributed to a glycolysis-dominant metabolism. The silencing of SRSF3 in human colon cancer cells induced a marked growth inhibition in both in vitro and in vivo experiments and caused an increase in the PKM1/PKM2 ratio, thus resulting in a metabolic shift from glycolysis to oxidative phosphorylation. At the same time, the silenced cells were induced to undergo autophagy. SRSF3 contributed to PKM mRNA splicing by co-operating with PTBP1 and hnRNPA1, which was validated by the results of RNP immunoprecipitation (RIP) and immunoprecipitation (IP) experiments. These findings altogether indicated that SRSF3 as a PKM splicer played a positive role in cancer-specific energy metabolism.
机译：富含丝氨酸和精氨酸的剪接因子3（SRSF3）是富含SR的家族蛋白，在多种癌症中均具有致癌作用。但是，该功能的详细机制以前尚未阐明。在这里，我们表明SRSF3剪接器调节丙酮酸激酶的表达谱，丙酮酸激酶是糖酵解中的限速酶之一。大多数癌细胞主要表达丙酮酸激酶肌肉2（PKM2），以维持以糖酵解为主的能量代谢。 SRSF3以及另一种剪接蛋白，聚嘧啶束结合蛋白1（PTBP1）和异质核核糖核蛋白A1（hnRNPA1）的过表达在临床癌症样本中均支持以下观点：这些蛋白会降低丙酮酸激酶肌肉1（PKM1）/ PKM2比例，对糖酵解占优势的代谢有积极作用。在体外和体内实验中，人结肠癌细胞中SRSF3的沉默均引起明显的生长抑制，并导致PKM1 / PKM2比值增加，从而导致代谢从糖酵解转变为氧化磷酸化。同时，沉默的细胞被诱导自噬。 SRSF3通过与PTBP1和hnRNPA1的协作而促进了PKM mRNA的剪接，这已通过RNP免疫沉淀（RIP）和免疫沉淀（IP）实验的结果得到验证。这些发现完全表明，SRSF3作为PKM剪接物在癌症特异性能量代谢中发挥了积极作用。

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