PMID- 30423573
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20210526
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 50
IP  - 6
DP  - 2018
TI  - MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway 
      Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in 
      Ovalbumin-Induced Asthmatic Mice.
PG  - 2365-2389
LID - 10.1159/000495097 [doi]
AB  - BACKGROUND/AIMS: The etiology of asthma, which is a complicated disorder with 
      various symptoms, including wheezing, coughing, and airflow obstruction, remains 
      poorly understood. In addition, the effects of microRNAs (miRs) have not been 
      explored. This study explored the effect of microRNA-200a (miR-200a) on airway 
      smooth muscle cells (ASMCs) and airway remodeling in asthmatic mice. Furthermore, 
      we speculated that miR-200a achieves its effect by targeting FOXC1 via the 
      PI3K/AKT signaling pathway based on differentially expressed gene screening, 
      target miR predictions and a bioinformatics analysis. METHODS: Eighty mice were 
      assigned to a saline group or an ovalbumin (OVA) group, and the OVA group was 
      transfected with a series of inhibitors, activators, and siRNAs to test the 
      established mouse model. Airway reactivity and the ratio of eosinophils (EOSs) to 
      leukocytes were detected. An ELISA was adopted to measure the levels of 
      interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and immunoglobulin 
      E (IgE). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) 
      and western blotting were used to determine the expression of FOXC1, PI3K, AKT, 
      NF-kappaB, cyclin D1, TGF-beta1 and p-AKT in ASMCs. Finally, CCK-8 assays were performed 
      to detect cell proliferation and flow cytometry to detect apoptosis and cell 
      cycle entry. RESULTS: The bioinformatics analysis indicated that miR-200a 
      mediated the PI3K/AKT signaling pathway by targeting FOXC1. In addition, mouse 
      models of asthma were established. An elevated expression of miR-200a, a 
      decreased mRNA and protein expression of FOXC1, PI3K, AKT, NF-kappaB, cyclin D1 and 
      TGF-beta1, a decreased expression of p-AKT, suppressed cell proliferation, 
      accelerated apoptosis, and an increased number of cells at the G0/G1 phase were 
      observed following the upregulation of miR-200a and downregulation of FOXC1. 
      CONCLUSION: The overexpression of miR-200a may downregulate FOXC1, thereby 
      inhibiting the activation of the PI3K/AKT signaling pathway and ultimately 
      suppressing ASMC proliferation and airway remodeling in asthmatic mice. This 
      evidence supports the potential that miR-200a represents a new approach to 
      treating asthma.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Liu, Ying
AU  - Liu Y
FAU - Miao, Yi
AU  - Miao Y
FAU - Gao, Xin
AU  - Gao X
FAU - Wang, Yuan-Yuan
AU  - Wang YY
FAU - Wang, Huan
AU  - Wang H
FAU - Zheng, Ya-Wen
AU  - Zheng YW
FAU - Zhao, Zhi-Yuan
AU  - Zhao ZY
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20181113
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Antagomirs)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxc1 protein, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn200 microRNA, mouse)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
RIN - Cell Physiol Biochem. 2021;55(1):139. PMID: 34037344
MH  - *Airway Remodeling
MH  - Animals
MH  - Antagomirs/metabolism
MH  - Asthma/*etiology/immunology/metabolism
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Female
MH  - Forkhead Transcription Factors/antagonists & inhibitors/genetics/*metabolism
MH  - G1 Phase Cell Cycle Checkpoints
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - MicroRNAs/antagonists & inhibitors/genetics/*metabolism
MH  - Myocytes, Smooth Muscle/cytology/metabolism
MH  - Ovalbumin/immunology
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
OTO - NOTNLM
OT  - Airway remodeling
OT  - Airway smooth muscle cell
OT  - Asthma
OT  - FOXC1
OT  - MicroRNA-200a
OT  - PI3K/AKT signaling pathway
EDAT- 2018/11/14 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/11/14 06:00
PHST- 2017/11/28 00:00 [received]
PHST- 2018/11/05 00:00 [accepted]
PHST- 2018/11/14 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/11/14 06:00 [entrez]
AID - 000495097 [pii]
AID - 10.1159/000495097 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2018;50(6):2365-2389. doi: 10.1159/000495097. Epub 2018 Nov 
      13.