Transcription factor c-Jun modulates GLUT1 in glycolysis and breast cancer metastasis.
Transcription factor c-Jun modulates GLUT1 in glycolysis and breast cancer metastasis.
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转录因子 c-Jun 在糖酵解和乳腺癌转移中调节 GLUT1
DOI：
10.1186/s12885-022-10393-x
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发表时间：
2022-12-07
期刊：
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
作者：
作为膜葡萄糖转运蛋白（GLUT）的主要亚型，GLUT 1与多种肿瘤的发生、转移和预后有关。然而，其在乳腺癌转移中的作用仍有待阐明。在这里，我们检查了来自几个独立数据库的乳腺癌患者的转录和生存数据，包括Oncomine，基因表达谱交互分析，正常和肿瘤组织的基因表达，UALCAN，cBioPortal，Kaplan-Meier Plotter和PROGgeneV 2。我们发现它的mRNA在癌组织中表达显著升高，这与转移和生存率低有关。转录因子c-Jun可能与GLUT 1启动子结合，下调其基因表达或mRNA稳定性，从而抑制糖酵解和转移。通过qRT-PCR，我们验证了GLUT 1在38对人乳腺癌样本中显著增加，而JUN降低。免疫组化结果显示，GLUT 1在肿瘤组织中的表达水平高于正常组织。为了探索潜在的途径，我们进一步对GLUT 1和JUN相关基因进行了GO和KEGG分析，发现乳腺癌组织中GLUT 1通过转录因子c-Jun增加，从而影响糖酵解和乳腺癌转移。
As the main isoforms of membranous glucose transporters (GLUT), GLUT1 involves tumorigenesis, metastasis and prognosis in a variety of cancers. However, its role in breast cancer metastasis remains to be elucidated. Here we examined its transcriptional and survival data in patients with breast cancer from several independent databases including the Oncomine, Gene Expression Profiling Interactive Analysis, Gene Expression across Normal and Tumor tissue, UALCAN, cBioPortal, Kaplan-Meier Plotter and PROGgeneV2. We found that its mRNA expression was significantly high in cancer tissues, which was associated with metastasis and poor survival. Transcription factor c-Jun might bind to GLUT1 promoter to downregulate its gene expression or mRNA stability, therefore to suppress glycolysis and metastasis. By qRT-PCR, we verified that GLUT1 was significantly increased in 38 paired human breast cancer samples while JUN was decreased. Furthermore, the protein level of GLUT1 was higher in tumor than in normal tissues by IHC assay. To explore underlying pathways, we further performed GO and KEGG analysis of genes related to GLUT1 and JUN and found that GLUT1 was increased by transcription factor c-Jun in breast cancer tissues to influence glycolysis and breast cancer metastasis.
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