PMID- 36030691
OWN - NLM
STAT- MEDLINE
DCOM- 20221021
LR  - 20221021
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 112
DP  - 2022 Nov
TI  - Circular RNA circESPL1 knockdown alleviates lipopolysaccharide (LPS)-induced lung 
      cell injury via sponging miR-326 to regulate MAPK14.
PG  - 109146
LID - S1567-5769(22)00630-0 [pii]
LID - 10.1016/j.intimp.2022.109146 [doi]
AB  - BACKGROUND: Infantile pneumonia (IP) is a common inflammatory disease, which 
      brings a heavy burden to young children's health. Previous studies suggested that 
      circular RNA (circRNA) hsa_circ_0026579 (also called circESPL1) was significantly 
      upregulated in pneumonia patients, which was associated with the disease 
      severity. This subject aimed to explore the functional effects and potential 
      regulatory mechanism of circESPL1 on lipopolysaccharide (LPS)-induced lung cell 
      injury. METHODS: WI-38 and MRC-5 cells were stimulated by LPS to mimic the 
      inflammatory injury model. CircESPL1, microRNA-326 (miR-326), and 
      Mitogen-Activated Protein Kinase 14 (MAPK14)levels were measured using real-time 
      quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), 
      5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays were performed to 
      assess cell proliferation and apoptosis. Western blot analysis of B-cell 
      lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), C-caspase 3, and MAPK14 
      protein levels. Tumor necrosis factor-alpha (TNF-alpha), Interleukin-6 (IL-6), and IL-1beta 
      levels were examined using an Enzyme-linked immunosorbent assay (ELISA). Using 
      Starbase analysis, the binding between miR-326 and circESPL1 or MAPK14 was 
      predicted, followed by confirmation using a dual-luciferase reporter and RNA 
      Immunoprecipitation (RIP) assays. RESULTS: Increased circESPL1 and MAPK14, and 
      reduced miR-326 were observed in serum samples from preeclampsia sufferers and 
      LPS-treated lung cells (P < 0.05). Furthermore, circESPL1 deficiency overturned 
      LPS-mediated cell proliferation, apoptosis, and inflammatory response in vitro 
      (P < 0.05). In terms of molecular mechanisms, circESPL1 worked as a sponge of 
      miR-326, and miR-326 absence reversed the protective role of circESPL1 silencing 
      on LPS-triggered lung cell injury (P < 0.05). Also, miR-326 directly targeted 
      MAPK14, and MAPK14 overexpression abolished miR-326-mediated impacts under LPS 
      treatment (P < 0.05). CONCLUSION: CircESPL1 knockdown might attenuate LPS-caused 
      lung cell injury by regulating the miR-326/ MAPK14 axis, providing useful insight 
      for exploring a novel therapeutic approach for IP.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Liang, Yamei
AU  - Liang Y
AD  - Department of Pediatrics, Taizhou First People's Hospital, China.
FAU - Miao, Yingying
AU  - Miao Y
AD  - Department of Pediatrics, Taizhou First People's Hospital, China.
FAU - Xiang, Jingjing
AU  - Xiang J
AD  - Department of Pediatrics, Taizhou First People's Hospital, China. Electronic 
      address: vastmind@163.com.
LA  - eng
PT  - Journal Article
DEP - 20220826
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 3.4.22.- (Caspase 3)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN326 microRNA, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
RN  - 0 (RNA, Circular)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Humans
MH  - Apoptosis/genetics
MH  - bcl-2-Associated X Protein
MH  - Caspase 3
MH  - Interleukin-6
MH  - Lipopolysaccharides/adverse effects
MH  - Lung/pathology
MH  - *Lung Injury/chemically induced/genetics/pathology
MH  - *MicroRNAs/genetics
MH  - *Mitogen-Activated Protein Kinase 14/metabolism
MH  - Pneumonia/metabolism
MH  - *RNA, Circular/genetics
MH  - Tumor Necrosis Factor-alpha
MH  - Cell Line
OTO - NOTNLM
OT  - Infantile pneumonia
OT  - LPS
OT  - MAPK14
OT  - circESPL1
OT  - miR-326
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/08/29 06:00
MHDA- 2022/10/21 06:00
CRDT- 2022/08/28 18:15
PHST- 2022/04/29 00:00 [received]
PHST- 2022/07/25 00:00 [revised]
PHST- 2022/08/05 00:00 [accepted]
PHST- 2022/08/29 06:00 [pubmed]
PHST- 2022/10/21 06:00 [medline]
PHST- 2022/08/28 18:15 [entrez]
AID - S1567-5769(22)00630-0 [pii]
AID - 10.1016/j.intimp.2022.109146 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2022 Nov;112:109146. doi: 10.1016/j.intimp.2022.109146. Epub 
      2022 Aug 26.