PMID- 34929342
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20220210
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 813
DP  - 2022 Mar 1
TI  - IRF4 transcriptionally activate HOTAIRM1, which in turn regulates IRF4 
      expression, thereby affecting Th9 cell differentiation and involved in allergic 
      rhinitis.
PG  - 146118
LID - S0378-1119(21)00713-7 [pii]
LID - 10.1016/j.gene.2021.146118 [doi]
AB  - BACKGROUND: Allergic rhinitis (AR) is an inflammatory reaction caused by 
      irritation of nasal mucosa by external allergens, which seriously affects the 
      life of patients. Here, we aimed to investigate the effect and mechanism of long 
      non-coding RNA HOX antisense intergenic RNA myeloid 1 (lncRNA HOTAIRM1) on AR 
      development. METHODS: The nasal mucosa samples were collected from AR patients 
      and AR model mice (induced by ovalbumin). T helper type 9 (Th9) cells were 
      examined by flow cytometry. Fluorescence in situ hybridization was conducted to 
      examine the localization of HOTAIRM1 in CD4(+) T cells. Dual-luciferase reporter 
      assay or RNA immunoprecipitation was conducted to examine the bond between 
      HOTAIRM1 and miR-148a-3p, miR-148a-3p, and interferon regulatory factor 4 (IRF4). 
      Chromatin Immunoprecipitation assay was conducted to detect the interaction 
      between IRF4 and HOTAIRM1 promoter. RESULTS: HOTAIRM1, interleukin-9 (IL-9), and 
      IRF4 were highly expressed in the AR model. The ratio of Th9 cells was increased 
      in AR mice and overexpressing HOTAIRM1 further promoted Th9 cell differentiation, 
      while the effect was reversed after overexpression of miR-148a-3p. Besides, in 
      vivo experiments showed that interfering with HOTAIRM1 reduced the number of 
      sneezing and rubbing movements, reduced immunoglobulin E (IgE) and IL-9 levels, 
      as well as Th9 cells. HOTAIRM1 was expressed in the cytoplasm and the 
      interactions between HOTAIRM1 and miR-148a-3p, miR-148a-3p and IRF4, were 
      confirmed. Furthermore, IRF4 bound to the HOTAIRM1 promoter and promoted its 
      transcriptional activation. CONCLUSION: HOTAIRM1 was highly expressed in the AR 
      model. Besides, IRF4 activated HOTAIRM1 transcription, and HOTAIRM1, in turn, 
      up-regulated IRF4 expression through competitively binding to miR-148a-3p with 
      IRF4, thereby affecting Th9 cell differentiation and participating in the 
      occurrence and development of AR. Our results suggested that interference with 
      HOTAIRM1 might become a treatment for AR.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Li, Lihua
AU  - Li L
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
FAU - Deng, Jianjian
AU  - Deng J
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
FAU - Huang, Taojian
AU  - Huang T
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
FAU - Liu, Ke
AU  - Liu K
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
FAU - Jiang, Xunshuo
AU  - Jiang X
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
FAU - Chen, Xubo
AU  - Chen X
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
FAU - Yang, Chunping
AU  - Yang C
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Nanchang University, Nanchang 330006, People's Republic of China. 
      Electronic address: ycp406@sohu.com.
LA  - eng
PT  - Journal Article
DEP - 20211218
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (interferon regulatory factor-4)
RN  - 0 (long non-coding RNA HOTAIRM1, human)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cell Differentiation/genetics
MH  - Cell Proliferation/genetics
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Inflammation/genetics
MH  - Interferon Regulatory Factors/biosynthesis/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - MicroRNAs/*genetics/metabolism
MH  - Nasal Mucosa/immunology
MH  - RNA, Long Noncoding/genetics
MH  - Rhinitis, Allergic/*genetics/metabolism/pathology
MH  - Signal Transduction/genetics
MH  - T-Lymphocytes, Helper-Inducer/metabolism/physiology
MH  - Transcriptome
OTO - NOTNLM
OT  - Allergic rhinitis
OT  - IRF4
OT  - Mir-148a-3p
OT  - Th9 cells
OT  - lncrna HOTAIRM1
EDAT- 2021/12/21 06:00
MHDA- 2022/02/11 06:00
CRDT- 2021/12/20 20:16
PHST- 2021/09/25 00:00 [received]
PHST- 2021/11/20 00:00 [revised]
PHST- 2021/12/06 00:00 [accepted]
PHST- 2021/12/21 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2021/12/20 20:16 [entrez]
AID - S0378-1119(21)00713-7 [pii]
AID - 10.1016/j.gene.2021.146118 [doi]
PST - ppublish
SO  - Gene. 2022 Mar 1;813:146118. doi: 10.1016/j.gene.2021.146118. Epub 2021 Dec 18.