PMID- 36229925
OWN - NLM
STAT- MEDLINE
DCOM- 20221229
LR  - 20221229
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 47
IP  - 1
DP  - 2023 Jan
TI  - Long noncoding RNA THRIL promotes foam cell formation and inflammation in 
      macrophages.
PG  - 156-166
LID - 10.1002/cbin.11934 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) and heterogenous nuclear ribonucleoprotein L 
      (hnRNPL)-related immunoregulatory lincRNA (THRIL) is a long noncoding RNA 
      (lncRNA) involved in various inflammatory diseases. However, its role in 
      atherosclerosis is not known. In this study, we aimed to investigate the function 
      of THRIL in mediating macrophage inflammation and foam cell formation. The 
      expression of THRIL was quantified in THP-1 macrophages after treatment with 
      oxidized low-density lipoprotein (oxLDL). The effect of THRIL overexpression and 
      knockdown on oxLDL-induced inflammatory responses and lipid accumulation was 
      determined. THRIL-associated protein partners were identified by RNA pull-down 
      and RNA immunoprecipitation assays. We show that THRIL is upregulated in 
      macrophages after oxLDL treatment. Knockdown of THRIL blocks oxLDL-induced 
      expression of interleukin-1beta (IL-1beta), IL-6, and TNF-alpha and lipid accumulation. 
      Conversely, ectopic expression of THRIL enhances inflammatory gene expression and 
      lipid deposition in oxLDL-treated macrophages. Moreover, THRIL depletion 
      increases cholesterol efflux from macrophages and the expression of ATP-binding 
      cassette transporter (ABC) A1 and ABCG1. FOXO1 is identified as a protein partner 
      of THRIL and promotes macrophage inflammation and lipid accumulation. 
      Furthermore, overexpression of FOXO1 restores lipid accumulation and inflammatory 
      cytokine production in THRIL-depleted macrophages. In conclusion, our data 
      suggest a model where THRIL interacts with FOXO1 to promote macrophage 
      inflammation and foam cell formation. THRIL may represent a therapeutic target 
      for atherosclerosis.
CI  - (c) 2022 International Federation for Cell Biology.
FAU - Song, Xiaosu
AU  - Song X
AD  - Department of Cardiology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, China.
FAU - Gao, Fen
AU  - Gao F
AD  - Department of Cardiology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, China.
FAU - Li, Hong
AU  - Li H
AD  - Department of Cardiology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, China.
FAU - Qin, Weiwei
AU  - Qin W
AD  - Department of Cardiology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, China.
FAU - Chai, Chanjuan
AU  - Chai C
AD  - Department of Cardiology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, China.
FAU - Shi, Guojuan
AU  - Shi G
AD  - Department of Cardiology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, China.
FAU - Yang, Huiyu
AU  - Yang H
AUID- ORCID: 0000-0002-3557-2952
AD  - Department of Cardiology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, China.
LA  - eng
GR  - 20210302124416/Basic Research Program of Shanxi Province (Free Exploration) of 
      China/
GR  - 20220043/Science and Technology Grant for Selected Returned Chinese Scholars of 
      Shanxi Province of China/
PT  - Journal Article
DEP - 20221013
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Humans
MH  - *Atherosclerosis/metabolism
MH  - ATP Binding Cassette Transporter 1/metabolism
MH  - Cholesterol/metabolism
MH  - *Foam Cells/metabolism
MH  - *Inflammation/metabolism
MH  - *Lipoproteins, LDL/metabolism
MH  - Macrophages/metabolism
MH  - *RNA, Long Noncoding/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Gene Knockdown Techniques
OTO - NOTNLM
OT  - FOXO1
OT  - atherosclerosis
OT  - cholesterol efflux
OT  - inflammation
OT  - lipid accumulation
EDAT- 2022/10/15 06:00
MHDA- 2022/12/22 06:00
CRDT- 2022/10/14 00:42
PHST- 2022/07/31 00:00 [received]
PHST- 2022/09/13 00:00 [accepted]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2022/12/22 06:00 [medline]
PHST- 2022/10/14 00:42 [entrez]
AID - 10.1002/cbin.11934 [doi]
PST - ppublish
SO  - Cell Biol Int. 2023 Jan;47(1):156-166. doi: 10.1002/cbin.11934. Epub 2022 Oct 13.