PMID- 32852789
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20220102
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 162
IP  - 1
DP  - 2021 Jan
TI  - MicroRNA-7 negatively regulates Toll-like receptor 4 signaling pathway through 
      FAM177A.
PG  - 44-57
LID - 10.1111/imm.13252 [doi]
AB  - Toll-like receptor (TLR) 4 signalling is critical for innate immunoinflammatory 
      response and widely triggers the development of various types of clinical 
      diseases. MicroRNA-7 (miR-7) is well documented to play an important regulatory 
      role in various biological events. However, the exact role of miR-7 in TLR4 
      signalling pathway remains to be fully elucidated. In the present study, we found 
      that miR-7 expression in TLR4 signalling-activated bone marrow-derived 
      macrophages (BMDMs) stimulated by LPS was dramatically increased. Importantly, 
      miR-7 deficiency significantly enhanced the production of related inflammatory 
      cytokines including IL-1beta, IL-6 and IL-12, as well as TNF-alpha, on LPS-activated 
      BMDMs, accompanied by elevated transduction of TLR4 signalling including 
      Myd88-dependent and Myd88-independent pathways, whereas miR-7 overexpression 
      significantly decreased the transduction of TLR4 signalling and the production of 
      related inflammatory cytokines. Mechanistically, we identified family with 
      sequence similarity 177, member A (FAM177A) as a novel target molecule of miR-7. 
      Furthermore, down-regulation of FAM177A using RNAi could impair the transduction 
      of TLR4 signalling. Finally, down-regulation of FAM177A also reversed the effect 
      of miR-7 deficiency on TLR4 signalling transduction and production of related 
      inflammatory cytokines on BMDMs. Therefore, we provide the new evidence that 
      miR-7 acts as a novel negative fine-tuner in regulating TLR4 signalling pathways 
      by targeting FAM177A, which might throw light on the basal understanding on the 
      regulatory mechanism of TLR4 signalling and benefit the development of 
      therapeutic strategies against related clinical diseases.
CI  - (c) 2020 John Wiley & Sons Ltd.
FAU - Chen, Huizi
AU  - Chen H
AUID- ORCID: 0000-0002-8914-8428
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi, 
      China.
AD  - Department of Immunology, Zunyi Medical University, Zunyi, China.
FAU - Guo, Mengmeng
AU  - Guo M
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi, 
      China.
AD  - Department of Immunology, Zunyi Medical University, Zunyi, China.
FAU - Yue, Dongxu
AU  - Yue D
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi, 
      China.
AD  - Department of Immunology, Zunyi Medical University, Zunyi, China.
FAU - Zhao, Juanjuan
AU  - Zhao J
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi, 
      China.
AD  - Department of Immunology, Zunyi Medical University, Zunyi, China.
FAU - Zhou, Ya
AU  - Zhou Y
AD  - Department of Medical Physics, Zunyi Medical University, Zunyi, China.
FAU - Chen, Chao
AU  - Chen C
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi, 
      China.
AD  - Department of Immunology, Zunyi Medical University, Zunyi, China.
FAU - Liang, Guiyou
AU  - Liang G
AD  - Department of Cardiovascular Surgery, Affiliated Hospital of Guizhou Medical 
      University, Guiyang, China.
AD  - Department of Cardiovascular Surgery, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, China.
FAU - Xu, Lin
AU  - Xu L
AUID- ORCID: 0000-0002-6889-0279
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi, 
      China.
AD  - Department of Immunology, Zunyi Medical University, Zunyi, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201019
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Cytokines)
RN  - 0 (MIRN7 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cytokines/genetics
MH  - Down-Regulation/genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Inflammation/genetics
MH  - Macrophages/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics
MH  - Myeloid Differentiation Factor 88/genetics
MH  - RAW 264.7 Cells
MH  - Signal Transduction/*genetics
MH  - Toll-Like Receptor 4/*genetics
PMC - PMC7730018
OTO - NOTNLM
OT  - FAM177A
OT  - LPS
OT  - TLR4
OT  - macrophages
OT  - microRNA-7
COIS- All authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2020/08/28 06:00
MHDA- 2021/08/03 06:00
PMCR- 2022/01/01
CRDT- 2020/08/28 06:00
PHST- 2019/10/01 00:00 [received]
PHST- 2020/07/08 00:00 [revised]
PHST- 2020/08/12 00:00 [accepted]
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2020/08/28 06:00 [entrez]
PHST- 2022/01/01 00:00 [pmc-release]
AID - IMM13252 [pii]
AID - 10.1111/imm.13252 [doi]
PST - ppublish
SO  - Immunology. 2021 Jan;162(1):44-57. doi: 10.1111/imm.13252. Epub 2020 Oct 19.