PMID- 36811100
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230224
IS  - 1728-3043 (Print)
IS  - 2322-2921 (Electronic)
IS  - 1728-3043 (Linking)
VI  - 21
IP  - 1
DP  - 2023 Jan
TI  - The PBX1/miR-141-miR-200a/EGR2/SOCS3 Axis; Integrative Analysis of Interaction 
      Networks to Discover the Possible Mechanism of MiR-141 and MiR-200a-Mediated Th17 
      Cell Differentiation.
PG  - e3211
LID - 10.30498/ijb.2022.317078.3211 [doi]
AB  - BACKGROUND: Overexpression of miR-141 and miR-200a is known to be associated with 
      the differentiation of T helper 17 (Th17) cells, which are key players in the 
      pathophysiology of autoimmune disorders. However, the function and governing 
      mechanism of these two microRNAs (miRNAs) in Th17 cell skewing are poorly 
      defined. OBJECTIVES: The aim of the present study was to identify the common 
      upstream transcription factors and downstream target genes of miR-141 and 
      miR-200a to obtain a better insight into the possible dysregulated molecular 
      regulatory networks driving miR-141/miR-200a-mediated Th17 cell development. 
      MATERIALS AND METHODS: A consensus-based prediction strategy was applied for 
      in-silico identification of potential transcription factors and putative gene 
      targets of miR-141 and miR-200a. Thereafter, we analyzed the expression patterns 
      of candidate transcription factors and target genes during human Th17 cell 
      differentiation by quantitative real-time PCR and examined the direct interaction 
      between both miRNAs and their potential target sequences using dual-luciferase 
      reporter assays. RESULTS: According to our miRNA-based and gene-based interaction 
      network analyses, pre-B cell leukemia homeobox (PBX1) and early growth response 2 
      (EGR2) were respectively taken into account as the potential upstream 
      transcription factor and downstream target gene of miR-141 and miR-200a. There 
      was a significant overexpression of the PBX1 gene during the Th17 cell induction 
      period. Furthermore, both miRNAs could directly target EGR2 and inhibit its 
      expression. As a downstream gene of EGR2, the suppressor of cytokine signaling 3 
      (SOCS3) was also downregulated during the differentiation process. CONCLUSIONS: 
      These results indicate that activation of the PBX1/miR-141-miR-200a/EGR2/SOCS3 
      axis may promote Th17 cell development and, therefore, trigger or exacerbate 
      Th17-mediated autoimmunity.
CI  - Copyright: (c) 2021 The Author(s); Published by Iranian Journal of Biotechnology.
FAU - Bahmani, Leila
AU  - Bahmani L
AD  - Department of Stem Cells and Regenerative Medicine, Institute for Medical 
      Biotechnology, National Institute of Genetic Engineering and Biotechnology 
      (NIGEB), Tehran, Iran.
FAU - Baghi, Masoud
AU  - Baghi M
AD  - Department of Cell and Molecular Biology and Microbiology, Faculty of Biological 
      Science and Technology, University of Isfahan, Isfahan, Iran.
AD  - Department of Animal Biotechnology, Cell Science Research Center, Royan Institute 
      for Biotechnology, ACECR, Isfahan, Iran.
FAU - Peymani, Maryam
AU  - Peymani M
AD  - Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad 
      University, Shahrekord, Iran.
FAU - Javeri, Arash
AU  - Javeri A
AD  - Department of Stem Cells and Regenerative Medicine, Institute for Medical 
      Biotechnology, National Institute of Genetic Engineering and Biotechnology 
      (NIGEB), Tehran, Iran.
FAU - Ghaedi, Kamran
AU  - Ghaedi K
AD  - Department of Cell and Molecular Biology and Microbiology, Faculty of Biological 
      Science and Technology, University of Isfahan, Isfahan, Iran.
LA  - eng
PT  - Journal Article
DEP - 20230101
PL  - Iran
TA  - Iran J Biotechnol
JT  - Iranian journal of biotechnology
JID - 101276796
PMC - PMC9938929
OTO - NOTNLM
OT  - Autoimmunity
OT  - EGR2
OT  - MiR-141
OT  - MiR-200a
OT  - PBX1
OT  - T helper 17 cells
COIS- The authors declare that there is no conflict of interest regarding the 
      publication of this article.
EDAT- 2023/02/23 06:00
MHDA- 2023/02/23 06:01
PMCR- 2023/01/01
CRDT- 2023/02/22 15:15
PHST- 2021/11/28 00:00 [received]
PHST- 2022/03/06 00:00 [accepted]
PHST- 2023/02/22 15:15 [entrez]
PHST- 2023/02/23 06:00 [pubmed]
PHST- 2023/02/23 06:01 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - IJB-21-1 [pii]
AID - 10.30498/ijb.2022.317078.3211 [doi]
PST - epublish
SO  - Iran J Biotechnol. 2023 Jan 1;21(1):e3211. doi: 10.30498/ijb.2022.317078.3211. 
      eCollection 2023 Jan.