PMID- 33028811
OWN - NLM
STAT- MEDLINE
DCOM- 20210513
LR  - 20211007
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 10
DP  - 2020 Oct 7
TI  - CircRNA_09505 aggravates inflammation and joint damage in collagen-induced 
      arthritis mice via miR-6089/AKT1/NF-kappaB axis.
PG  - 833
LID - 10.1038/s41419-020-03038-z [doi]
LID - 833
AB  - A number of circular RNAs (circRNAs) have been implicated in rheumatoid arthritis 
      (RA) pathogenesis; however, little is known about their function and hidden 
      molecular mechanism in immune and inflammation regulation. We investigated the 
      role and the underlying mechanism of circRNA_09505 in RA in this study. Real-time 
      PCR and fluorescence in situ hybridization (FISH) are adopted to estimate the 
      quantitative expression and localization of circRNA_09505 in macrophages. The 
      altering effect of circRNA_09505 on inflammation is investigated in vitro and in 
      vivo by use of macrophage cell models and collagen-induced arthritis (CIA) mice. 
      Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) are 
      used to confirm the circRNA_09505/miR-6089 ceRNA network predicted by 
      bioinformatics analysis. Compared with controls, the expression of circRNA_09505 
      is upregulated in peripheral blood mononuclear cells (PBMCs) from patients with 
      RA. The proliferation and cell cycle are significantly promoted when 
      circRNA_09505 is upregulated in macrophages, whereas knockdown of circRNA_09505 
      inhibits macrophage proliferation and cell- cycle progression. Besides, 
      circRNA_09505 can act as a miRNA sponge for miR-6089 in macrophages, and promote 
      the production of TNF-alpha, IL-6, and IL-12 through ceRNA mechanism. Moreover, AKT1 
      is a direct target of miR-6089. CircRNA_09505 can promote AKT1 expression by 
      acting as a miR-6089 sponge via IkappaBalpha/NF-kappaB signaling pathway in macrophages. Most 
      interestingly, knockdown of circRNA_09505 significantly alleviates arthritis and 
      inflammation in vivo in CIA mice. These data support the hypothesis that 
      circRNA_09505 can function as a miR-6089 sponge and regulate inflammation via 
      miR-6089/AKT1/NF-kappaB axis in CIA mice.
FAU - Yang, Jinghan
AU  - Yang J
AD  - Department of Rheumatology & Central Laboratory of the First Affiliated Hospital, 
      Weifang Medical University, Weifang, 261053, China.
FAU - Cheng, Min
AU  - Cheng M
AD  - Department of Physiology, Clinical Medicine College, Weifang Medical University, 
      Weifang, 261053, China.
FAU - Gu, Bingjie
AU  - Gu B
AD  - Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing 
      Medical University, Nanjing, 210006, China.
FAU - Wang, Jinghua
AU  - Wang J
AD  - Department of Rheumatology & Central Laboratory of the First Affiliated Hospital, 
      Weifang Medical University, Weifang, 261053, China.
FAU - Yan, Shushan
AU  - Yan S
AD  - Department of Gastrointestinal and Anal Diseases Surgery of the Affiliated 
      Hospital, Weifang Medical University, Weifang, 261053, China. 
      yanshushan@wfmc.edu.cn.
FAU - Xu, Donghua
AU  - Xu D
AD  - Department of Rheumatology & Central Laboratory of the First Affiliated Hospital, 
      Weifang Medical University, Weifang, 261053, China. xudh@wfmc.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201007
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (RNA, Circular)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/chemically induced/*metabolism/pathology
MH  - Arthritis, Rheumatoid/chemically induced/*metabolism/pathology
MH  - Cell Proliferation/physiology
MH  - Collagen/pharmacology
MH  - Inflammation/*blood
MH  - Leukocytes, Mononuclear/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Circular/*blood
MH  - Signal Transduction/drug effects
PMC - PMC7542153
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/10/09 06:00
MHDA- 2021/05/14 06:00
PMCR- 2020/10/07
CRDT- 2020/10/08 05:28
PHST- 2020/05/24 00:00 [received]
PHST- 2020/09/21 00:00 [accepted]
PHST- 2020/09/17 00:00 [revised]
PHST- 2020/10/08 05:28 [entrez]
PHST- 2020/10/09 06:00 [pubmed]
PHST- 2021/05/14 06:00 [medline]
PHST- 2020/10/07 00:00 [pmc-release]
AID - 10.1038/s41419-020-03038-z [pii]
AID - 3038 [pii]
AID - 10.1038/s41419-020-03038-z [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Oct 7;11(10):833. doi: 10.1038/s41419-020-03038-z.