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MAPK and NF‐κB signalling pathways regulate the expression of miRNA, let‐7f in human endocervical epithelial cells
Author(s) -
Ayyar Kanchana K.,
Reddy Kudumula V. R.
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26665
Subject(s) - mapk/erk pathway , transactivation , microbiology and biotechnology , transcription factor , tlr3 , innate immune system , microrna , nf κb , p38 mitogen activated protein kinases , biology , signal transduction , kinase , immune system , cancer research , gene , toll like receptor , immunology , genetics
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‐κB) 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‐κB 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‐κB. Of these MAPK/ p38 and JNK directly influence the expression of let‐7f in End1/E6E7 cells. Inhibition of ERK and NF‐κB up regulates the expression of let‐7f and its transcription factor, C/EBPβ. In conclusion, we have identified a system through which TLR3 mediated immune response is regulated by C/EBPβ and let‐7f through the temporal activation of MAPK and NF‐κB in human endocervical cells.