PFKFB4 promotes lung adenocarcinoma progression via phosphorylating and activating transcriptional coactivator SRC-2.

PFKFB4 promotes lung adenocarcinoma progression via phosphorylating and activating transcriptional coactivator SRC-2.
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PFKFB 4通过磷酸化和激活转录辅激活因子SRC-2促进肺腺癌进展。

DOI:
10.1186/s12890-021-01420-x
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发表时间:
2021-02-16
影响因子:
3.1
通讯作者:
Han Z
Han Z
中科院分区:
医学3区
文献类型:
--
作者:
Meng J;Chen X;Han Z

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探讨6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶4(PFKFB 4)在肺腺癌中的作用及其可能机制。采用免疫共沉淀法分析PFKFB 4与SRC-2的相互作用。Western blot检测PFKFB 4基因敲除后,类固醇受体辅激活因子2(SRC-2)的磷酸化情况。进行转录组测序以找到SRC-2的下游靶标。采用CCK-8法、transwell法和transwell-matrigel法检测不同处理后A549和NCI-H1975细胞的增殖、迁移和侵袭能力。在我们的研究中,我们发现PFKFB 4在肺腺癌中过表达,与SRC家族蛋白相关,并与SRC-2相互作用。PFKFB 4可使SRC-2的Ser 487位磷酸化,从而改变SRC-2的转录活性。在功能上,PFKFB 4通过磷酸化SRC-2促进肺腺癌细胞的增殖、迁移和侵袭。此外,我们确定CARM 1受SRC-2的转录调控,并参与肺腺癌进展的PFKFB 4-SRC-2轴。我们的研究表明PFKFB 4通过增强磷酸化SRC-2介导的CARM 1表达促进肺腺癌细胞增殖、迁移和侵袭。
To investigate the role and its potential mechanism of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) in lung adenocarcinoma. Co-immunoprecipitation was performed to analyze the interaction between PFKFB4 and SRC-2. Western blot was used to investigate the phosphorylation of steroid receptor coactivator-2 (SRC-2) on the condition that PFKFB4 was knockdown. Transcriptome sequencing was performed to find the downstream target of SRC-2. Cell Counting Kit-8 (CCK-8) assay, transwell assay and transwell-matrigel assay were used to examine the proliferation, migration and invasion abilities in A549 and NCI-H1975 cells with different treatment. In our study we found that PFKFB4 was overexpressed in lung adenocarcinoma associated with SRC family protein and had an interaction with SRC-2. PFKFB4 could phosphorylate SRC-2 at Ser487, which altered SRC-2 transcriptional activity. Functionally, PFKFB4 promoted lung adenocarcinoma cells proliferation, migration and invasion by phosphorylating SRC-2. Furthermore, we identified that CARM1 was transcriptionally regulated by SRC-2 and involved in PFKFB4-SRC-2 axis on lung adenocarcinoma progression. Our research reveal that PFKFB4 promotes lung adenocarcinoma cells proliferation, migration and invasion via enhancing phosphorylated SRC-2-mediated CARM1 expression.
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