Differential Gene Expression Analysis Reveals Global LMTK2 Regulatory Network and Its Role in TGF-β1 Signaling.
Differential Gene Expression Analysis Reveals Global LMTK2 Regulatory Network and Its Role in TGF-β1 Signaling.
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DOI：
10.3389/fonc.2021.596861
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发表时间：
2021
影响因子：
4.7
通讯作者：
Swiatecka-Urban A
中科院分区：
文献类型：
--
作者：
Cruz DF;Mitash N;Mu F;Farinha CM;Swiatecka-Urban A
狐猴酪氨酸激酶2 （LMTK2）是一种跨膜丝氨酸/苏氨酸激酶，其作用已得到越来越多的认识；然而，与其他激酶相比，对LMTK2网络和生物学功能的了解仍然有限。最近的研究表明，转化生长因子(TGF)-β1在人支气管上皮细胞中通过调控LMTK2的内吞转运来调节其功能。在这里，我们旨在揭示LMTK2调控网络，并阐明其如何以TGF-β1依赖或独立的方式影响细胞功能和疾病通路。为了了解LMTK2和TGF-β1通路是如何相互联系的，我们在人支气管上皮cfbe410 -细胞中使用小（si）RNA介导的沉默来敲低（KD） LMTK2，用TGF-β1或对照处理细胞，并通过RNA测序（RNAseq）进行差异基因表达分析。在载体处理的细胞中，LMTK2 KD影响2506个基因的表达，而TGF-β1刺激后影响4162个基因的表达。生物信息学分析表明，LMTK2参与多种细胞功能和疾病途径，如细胞死亡和存活、细胞发育和癌症易感性。总之，我们的研究增加了目前对LMTK2网络及其与TGF-β1信号通路交叉的认识。这些发现将为未来探索预测的LMTK2相互作用和信号通路提供基础。
Lemur tyrosine kinase 2 (LMTK2) is a transmembrane Ser/Thr kinase whose role has been increasingly recognized; however, when compared to other kinases, understanding of the LMTK2 networks and biological functions is still limited. Recent data have shown that transforming growth factor (TGF)-β1 plays a role in modulating LMTK2 function by controlling its endocytic trafficking in human bronchial epithelial cells. Here, we aimed to unveil the LMTK2 regulatory network and elucidate how it affects cellular functions and disease pathways in either TGF-β1 dependent or independent manner. To understand how the LMTK2 and TGF-β1 pathways interconnect, we knocked down (KD) LMTK2 using small(si)RNA-mediated silencing in human bronchial epithelial CFBE41o- cells, treated cells with TGF-β1 or vehicle control, and performed differential gene expression analysis by RNA sequencing (RNAseq). In vehicle-treated cells, LMTK2 KD affected expression of 2,506 genes while it affected 4,162 genes after TGF-β1 stimulation. Bioinformatics analysis shows that LMTK2 is involved in diverse cellular functions and disease pathways, such as cell death and survival, cellular development, and cancer susceptibility. In summary, our study increases current knowledge about the LMTK2 network and its intersection with the TGF-β1 signaling pathway. These findings will serve as basis for future exploration of the predicted LMTK2 interactions and signaling pathways.
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影响因子：
3.7
作者：
Snodgrass SM;Cihil KM;Cornuet PK;Myerburg MM;Swiatecka-Urban A
通讯作者：
Swiatecka-Urban A
影响因子：
3.8
作者：
Harries LW;Perry JR;McCullagh P;Crundwell M
通讯作者：
Crundwell M
影响因子：
3.6
作者：
Bencze J;Mórotz GM;Seo W;Bencs V;Kálmán J;Miller CCJ;Hortobágyi T
通讯作者：
Hortobágyi T
影响因子：
4.7
作者：
Manser, Catherine;Vagnoni, Alessio;Miller, Christopher C. J.
通讯作者：
Miller, Christopher C. J.
DOI：
10.14800/ccm.1023
发表时间：
2015-01-01
期刊：
Cancer cell & microenvironment
影响因子：
--
作者：
Shah, Kalpit;Bradbury, Neil A
通讯作者：
Bradbury, Neil A