PURα Promotes the Transcriptional Activation of PCK2 in Oesophageal Squamous Cell Carcinoma Cells.
PURα Promotes the Transcriptional Activation of PCK2 in Oesophageal Squamous Cell Carcinoma Cells.
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PURα 促进食管鳞状细胞癌细胞中 PCK2 的转录激活
DOI：
10.3390/genes11111301
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发表时间：
2020-10-31
期刊：
影响因子：
3.5
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Sun Y;Gao J;Jing Z;Zhao Y;Sun Y;Zhao X
食管鳞状细胞癌（Esophageal squamous cell carcinoma，ESCC）以其局部浸润和远处转移的特点，成为胃肠道恶性肿瘤中致死率最高的肿瘤之一。嘌呤元件结合蛋白α（PURα）是一种DNA和RNA结合蛋白，近年来研究表明PURα的异常表达与某些肿瘤的进展有关，但其致癌功能，尤其是在食管鳞癌进展中的作用尚未确定。基于RNA-seq和ChIP-seq数据的生物信息学分析，我们发现PURα影响代谢途径，包括氧化磷酸化和脂肪酸代谢，我们观察到它在线粒体磷酸烯醇丙酮酸羧激酶（PCK 2）的启动子中有结合峰。同时，荧光素酶和ChIP-PCR/qPCR检测结果表明，PURα通过与GGGAGGCGGA基序结合，显著提高了PCK 2基因启动子的活性。Western blotting和qRT-PCR分析结果显示，PURα过表达可提高KYSE 510细胞中PCK 2的蛋白和mRNA水平，而PURα敲低则抑制KYSE 170细胞中PCK 2的蛋白和mRNA水平。此外，氧耗率（OCR）和胞外酸化率（ECAR）的测定结果表明，PURα促进ESCC细胞的代谢。总之，我们的结果有助于阐明PURα激活PCK 2转录和表达的分子机制，这有助于开发ESCC的新治疗靶点。
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal gastrointestinal malignancies due to its characteristics of local invasion and distant metastasis. Purine element binding protein α (PURα) is a DNA and RNA binding protein, and recent studies have showed that abnormal expression of PURα is associated with the progression of some tumors, but its oncogenic function, especially in ESCC progression, has not been determined. Based on the bioinformatic analysis of RNA-seq and ChIP-seq data, we found that PURα affected metabolic pathways, including oxidative phosphorylation and fatty acid metabolism, and we observed that it has binding peaks in the promoter of mitochondrial phosphoenolpyruvate carboxykinase (PCK2). Meanwhile, PURα significantly increased the activity of the PCK2 gene promoter by binding to the GGGAGGCGGA motif, as determined though luciferase assay and ChIP-PCR/qPCR. The results of Western blotting and qRT-PCR analysis showed that PURα overexpression enhances the protein and mRNA levels of PCK2 in KYSE510 cells, whereas PURα knockdown inhibits the protein and mRNA levels of PCK2 in KYSE170 cells. In addition, measurements of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) indicated that PURα promoted the metabolism of ESCC cells. Taken together, our results help to elucidate the molecular mechanism by which PURα activates the transcription and expression of PCK2, which contributes to the development of a new therapeutic target for ESCC.
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