PMID- 33505165
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220420
IS  - 1178-7007 (Print)
IS  - 1178-7007 (Electronic)
IS  - 1178-7007 (Linking)
VI  - 14
DP  - 2021
TI  - Downregulation of lncRNA EPB41L4A-AS1 Mediates Activation of MYD88-Dependent 
      NF-kappaB Pathway in Diabetes-Related Inflammation.
PG  - 265-277
LID - 10.2147/DMSO.S280765 [doi]
AB  - PURPOSE: Long non-coding RNAs (lncRNAs) have been shown to be involved in many 
      human diseases. In this study, we aimed to reveal the role and molecular 
      mechanism of lncRNA EPB41L4A-AS1 in type 2 diabetic mellitus (T2DM)-related 
      inflammation. METHODS: To explore the relationships between the expression of 
      EPB41L4A-AS1 and inflammatory factors in the blood of T2DM patients, we analyzed 
      peripheral blood mononuclear cell (PBMC) expression microarrays of T2DM patients 
      and expression microarrays of PBMC treated with lipopolysaccharide (LPS) from the 
      GEO database. The relationship between EPB41L4A-AS1 and phospho-p65 was explored 
      by Western blotting (WB) and immunofluorescence. The interactions between 
      EPB41L4A-AS1 and myeloid differentiation factor 88 (MYD88) were also verified 
      through quantitative real-time PCR, WB, and chromatin immunoprecipitation. 
      Glycolysis and mitochondrial stress were detected by Seahorse. RESULTS: 
      EPB41L4A-AS1 showed very low expression, which was significantly negatively 
      correlated with levels of inflammatory factors in PBMCs of T2DM patients and 
      PBMCs treated with LPS. These results were verified by cell experiments on PBMC 
      and THP-1 cells. Knockdown of EPB41L4A-AS1 led to the phosphorylation and nuclear 
      translocation of p65 and thus activated the NF-kappaB signaling pathway; it also 
      reduced the enrichment of H3K9me3 in the MYD88 promoter and increased expression 
      of MYD88. Overall, EPB41L4A-AS1 knockdown promoted the level of glycolysis and 
      ultimately enhanced the inflammatory response. CONCLUSION: EPB41L4A-AS1 knockdown 
      activated the NF-kappaB signaling pathway through a MYD88-dependent regulatory 
      mechanism, promoted glycolysis, and ultimately enhanced the inflammatory 
      response. These results demonstrate that EPB41L4A-AS1 is closely associated with 
      inflammation in T2DM, and that low expression of EPB41L4A-AS1 may be used as an 
      indicator of chronic inflammation and possible diabetic vascular complications in 
      T2DM patients.
CI  - (c) 2021 Wang et al.
FAU - Wang, Ziqing
AU  - Wang Z
AD  - School of Chemistry, Tsinghua University, Beijing 100084, People's Republic of 
      China.
AD  - State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International 
      Graduate School, Shenzhen 518055, People's Republic of China.
FAU - Liao, Weijie
AU  - Liao W
AD  - State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International 
      Graduate School, Shenzhen 518055, People's Republic of China.
AD  - Key Laboratory in Healthy Science and Technology, Division of Life Science, 
      Tsinghua Shenzhen International Graduate School, Shenzhen 518055, People's 
      Republic of China.
FAU - Liu, Fuhai
AU  - Liu F
AD  - State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International 
      Graduate School, Shenzhen 518055, People's Republic of China.
AD  - Department of Pathology, Xuzhou Medical University, Xuzhou 221104, People's 
      Republic of China.
FAU - Yang, Tingpeng
AU  - Yang T
AD  - State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International 
      Graduate School, Shenzhen 518055, People's Republic of China.
FAU - Xie, Weidong
AU  - Xie W
AD  - State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International 
      Graduate School, Shenzhen 518055, People's Republic of China.
AD  - Key Laboratory in Healthy Science and Technology, Division of Life Science, 
      Tsinghua Shenzhen International Graduate School, Shenzhen 518055, People's 
      Republic of China.
FAU - Liao, Meijian
AU  - Liao M
AD  - Key Laboratory in Healthy Science and Technology, Division of Life Science, 
      Tsinghua Shenzhen International Graduate School, Shenzhen 518055, People's 
      Republic of China.
AD  - Department of Pathology, Xuzhou Medical University, Xuzhou 221104, People's 
      Republic of China.
FAU - Gu, Dayong
AU  - Gu D
AD  - Department of Laboratory Medicine, Shenzhen Second People's Hospital, The First 
      Affiliated Hospital of Shenzhen University, Shenzhen 518035, People's Republic of 
      China.
FAU - Zhang, Yaou
AU  - Zhang Y
AD  - State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International 
      Graduate School, Shenzhen 518055, People's Republic of China.
AD  - Key Laboratory in Healthy Science and Technology, Division of Life Science, 
      Tsinghua Shenzhen International Graduate School, Shenzhen 518055, People's 
      Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210120
PL  - New Zealand
TA  - Diabetes Metab Syndr Obes
JT  - Diabetes, metabolic syndrome and obesity : targets and therapy
JID - 101515585
PMC - PMC7829128
OTO - NOTNLM
OT  - EPB41L4A-AS1
OT  - MYD88
OT  - NF-kappaB
OT  - diabetes
OT  - inflammation
COIS- The authors report no conflicts of interest in this work.
EDAT- 2021/01/29 06:00
MHDA- 2021/01/29 06:01
PMCR- 2021/01/20
CRDT- 2021/01/28 05:41
PHST- 2020/09/06 00:00 [received]
PHST- 2020/12/30 00:00 [accepted]
PHST- 2021/01/28 05:41 [entrez]
PHST- 2021/01/29 06:00 [pubmed]
PHST- 2021/01/29 06:01 [medline]
PHST- 2021/01/20 00:00 [pmc-release]
AID - 280765 [pii]
AID - 10.2147/DMSO.S280765 [doi]
PST - epublish
SO  - Diabetes Metab Syndr Obes. 2021 Jan 20;14:265-277. doi: 10.2147/DMSO.S280765. 
      eCollection 2021.