MAPK and NF-κB signalling pathways regulate the expression of miRNA, let-7f in human endocervical epithelial cells
MAPK and NF-κB signalling pathways regulate the expression of miRNA, let-7f in human endocervical epithelial cells
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DOI：
10.1002/jcb.26665
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发表时间：
2018-06-01
影响因子：
4
通讯作者：
Reddy, Kudumula V. R.
中科院分区：
文献类型：
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作者：
Ayyar, Kanchana K.;Reddy, Kudumula V. R.
microRNA（miRNAs）介导转录后基因抑制，是上皮免疫应答中复杂调控网络的关键组成部分。上皮细胞中miRNA基因的转录可通过Toll样受体（TLR）、活化B细胞核因子κ轻链增强子（NF-B）和丝裂原活化蛋白激酶（MAPK）途径进行精细调控，导致核转录因子相关的miRNA反式激活和反式阻遏。miRNA，let-7 f参与调节人子宫颈内细胞（End 1/E6 E7）中TLR 3刺激后的先天免疫应答，并且let-7 f减少与免疫活化不良相关。因此，let-7 f的表达受到严格控制。然而，let-7 f在这些细胞中的调节机制尚不清楚。因此，在本研究中，我们研究了MAPK和NF-B在let-7 f转录中的作用。我们报道了TLR 3的信号传导导致多种信号传导途径的激活，包括MAPK/ERK、JNK、p38和NF-B。其中MAPK/ p38和JNK直接影响End 1/E6 E7细胞let-7 f的表达。ERK和NF-B的抑制上调let-7 f及其转录因子C/EBP的表达。总之，我们已经确定了一个系统，通过该系统，TLR 3介导的免疫应答由C/EBP和let-7 f通过MAPK和NF-B在人宫颈管细胞中的时间激活来调节。
MicroRNAs (miRNAs) mediate post-transcriptional gene suppression and are a critical component of the complex regulatory networks in epithelial immune responses. Transcription of miRNA genes in epithelial cells can be elaborately controlled through Toll-like receptors (TLRs), and associated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) and mitogen-activated protein kinase (MAPK) pathways, leading to nuclear transcription factor associated-transactivation and transrepression of miRNAs. MiRNA, let-7f is involved in the regulation of innate immune responses post TLR3 stimulation in human endocervical cells (End1/E6E7) and decreased let-7f is associated with poor immune activation. Thus, expression of let-7f is under strict control. However, the mechanism by which let-7f is regulated in these cells is not known. Therefore, in the present study, we have investigated the role of MAPK and NF-B in the transcription of let-7f. We report that signalling of TLR3, results in activation of multiple signalling pathways including MAPK/ERK, JNK, p38, and NF-B. Of these MAPK/ p38 and JNK directly influence the expression of let-7f in End1/E6E7 cells. Inhibition of ERK and NF-B up regulates the expression of let-7f and its transcription factor, C/EBP. In conclusion, we have identified a system through which TLR3 mediated immune response is regulated by C/EBP and let-7f through the temporal activation of MAPK and NF-B in human endocervical cells.