PMID- 35410505
OWN - NLM
STAT- MEDLINE
DCOM- 20220610
LR  - 20221202
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 247
IP  - 11
DP  - 2022 Jun
TI  - Identification of a circRNA-mediated comprehensive ceRNA network in spinal cord 
      injury pathogenesis.
PG  - 931-944
LID - 10.1177/15353702221082929 [doi]
AB  - RNAs are closely associated with human diseases; however, immune-related genes 
      (IRGs) and their potential regulatory networks in relation to spinal cord injury 
      (SCI) are still poorly understood. Here, we investigated the key IRGs as well as 
      the competing endogenous RNA (ceRNA) mechanisms that are associated with SCI 
      pathogenesis based on microarray datasets and the use of a rat SCI model. 
      Specifically, four independent SCI microarray datasets from Gene Expression 
      Omnibus (GEO) database were analyzed and, thereafter, differentially expressed 
      IRGs were annotated via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and 
      Genomes (KEGG) analyses. Furthermore, based on the GEO datasets, differentially 
      expressed RNAs (DERNAs), including DEcircRNAs, DEmiRNAs, and DEmRNAs were 
      identified and interactions between them were also predicted using online 
      databases, and to construct a circular RNA (circRNA) mediated ceRNA network, 
      candidate RNAs were also identified. Furthermore, the support vector machine 
      (SVM) and least absolute shrinkage and selection operator (LASSO) methods were 
      used for the identification of critical DERNAs, while differential gene 
      expression was validated using the GSE20907 dataset. Our results were as follows. 
      In the SCI microarray datasets, 32, 58, and 74 DEIRGs, DEcircRNAs, and DEmiRNAs 
      were identified, respectively. In addition, GO and KEGG analyses showed that the 
      DEIRGs were primarily enriched in neutrophil-mediated immunity and nuclear 
      factor-kappa B (NF-kappaB) and hypoxia-inducible factor-1 (HIF-1) signaling pathways, 
      and based on LASSO and SVM screening, PLXNB2 was identified as a DEIRG, while 
      hsa_circ_0026646 was identified as the key circRNA, showing a higher SCI 
      expression. Furthermore, our results proved that PLXNB2 and hsa_circ_0026646 were 
      upregulated in SCI, whereas miR-331-3p was downregulated, and, interestingly, 
      similar expression profiles were confirmed using the rat SCI model. Furthermore, 
      fluorescent reporter assay indicated that both hsa_circ_0026646 and PLXNB2 have 
      miR-331-3p target sites, and the ceRNA hypothesis suggested the dysregulation of 
      hsa_circ_0026646, miR-331-3p, and PLXNB2 in SCI. Thus, our results suggested that 
      in SCI pathogenesis, hsa_circ_0026646 correlates with PLXNB2 by targeting 
      miR-331-3p.
FAU - Zu, Chao
AU  - Zu C
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710004, China.
AD  - Department of Surgical Oncology, Shaanxi Provincial People's Hospital, The 
      Affiliated Hospital of Northwestern Polytechnical University and Xi'an Jiaotong 
      University, Xi'an 710068, China.
FAU - Li, Jingyuan
AU  - Li J
AD  - Department of Orthopedics, Shaanxi Provincial People's Hospital, The Affiliated 
      Hospital of Northwestern Polytechnical University and Xi'an Jiaotong University, 
      Xi'an 710068, China.
FAU - He, Xijing
AU  - He X
AUID- ORCID: 0000-0002-0465-5376
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710004, China.
AD  - Orthopaedic Hospital, Xi'an International Rehabilitation Medical Center, Xi'an 
      710065, China.
FAU - Ji, Le
AU  - Ji L
AD  - Department of Orthopedics, Shaanxi Provincial People's Hospital, The Affiliated 
      Hospital of Northwestern Polytechnical University and Xi'an Jiaotong University, 
      Xi'an 710068, China.
FAU - Li, Xia
AU  - Li X
AD  - Basic Medical College, The Fourth Military Medical University, Xi'an 710032, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220411
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Gene Ontology
MH  - *MicroRNAs/genetics/metabolism
MH  - RNA, Circular/genetics
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - *Spinal Cord Injuries/genetics
PMC - PMC9189570
OTO - NOTNLM
OT  - GEO database
OT  - Spinal cord injury
OT  - circular RNA
OT  - competing endogenous RNA
OT  - immune-related genes
OT  - microRNA
COIS- Declaration of conflicting interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2022/04/13 06:00
MHDA- 2022/06/11 06:00
PMCR- 2022/12/01
CRDT- 2022/04/12 05:25
PHST- 2022/04/13 06:00 [pubmed]
PHST- 2022/06/11 06:00 [medline]
PHST- 2022/04/12 05:25 [entrez]
PHST- 2022/12/01 00:00 [pmc-release]
AID - 10.1177_15353702221082929 [pii]
AID - 10.1177/15353702221082929 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2022 Jun;247(11):931-944. doi: 10.1177/15353702221082929. 
      Epub 2022 Apr 11.