PPARGC1A is upregulated and facilitates lung cancer metastasis
PPARGC1A is upregulated and facilitates lung cancer metastasis
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DOI：
10.1016/j.yexcr.2017.08.017
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发表时间：
2017-10-15
影响因子：
3.7
通讯作者：
Zhao, Song
中科院分区：
文献类型：
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作者：
Li, Jin-dong;Feng, Qing-chuan;Zhao, Song
肺癌仍然是癌症相关死亡的主要原因，转移性进展仍然是肺癌死亡的最大单一原因。因此，确定可靠的肺癌预后生物标志物势在必行。我们进行了定量实时PCR（qRT-PCR）分析，以探讨上皮间质转化（EMT）诱导剂，调节EMT过程中的三个晚期肺癌患者的疾病。过氧化物酶体增殖物激活受体γ（PPARGC 1A）是所有三个人非小细胞肺癌（NSCLC）患者样本中最高的过表达基因。在人正常肺和转移性肺癌细胞系中的进一步评估揭示，PPARGC 1A的表达在转移性肺癌细胞系中上调。宏基因组学分析显示PPARGC 1A、锌指转录因子snail同系物1（SNAIL）和转移性肺疾病之间存在直接相关性。PPARGC 1A转录表达的上调独立于上游AMP依赖性蛋白激酶（AMPK）激活或沉默交配型信息调节2同源物1（SIRT 1）稳态表达的差异上调。异种移植物尾静脉定殖试验证明PPARGC 1A的高表达是肺癌向脑转移进展的先决条件。我们的研究结果表明PPARGC 1A可能是肺癌预后的潜在生物标志物。
Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAIL), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis.