PMID- 36534156
OWN - NLM
STAT- MEDLINE
DCOM- 20221228
LR  - 20231214
IS  - 1437-9813 (Electronic)
IS  - 0179-0358 (Linking)
VI  - 39
IP  - 1
DP  - 2022 Dec 19
TI  - Plasma exosomal miR-199a-3p downregulates cell proliferation and migration in 
      Hirschsprung's disease by targeting mTOR.
PG  - 54
LID - 10.1007/s00383-022-05337-2 [doi]
AB  - BACKGROUND: Plasma exosomal microRNAs have been suggested to be potential 
      biomarkers of disease. However, the exosomal microRNAs in Hirschsprung's disease 
      (HSCR) are still unclear. In this study, we analyzed the miRNA profiles of HSCR 
      and elucidated the mechanism of the selected miR-199a-3p in the development of 
      HSCR. METHODS: Plasma exosomes were isolated, and exosomal miRNA high-throughput 
      sequencing was performed to obtain differentially expressed miRNAs. CCK-8 and 
      Transwell assay were used to determine the function of the most differentially 
      expressed miRNA, which was confirmed in tissue specimen. Thereafter, target genes 
      of the selected miRNAs were predicted by the databases. Gene Ontology (GO) 
      analysis, Kyoto Encyclopedia of Genes Genomes (KEGG) analysis, and 
      protein-protein interaction network (PPI) construction of possible target genes 
      were used to perform enrichment analysis and interaction. Finally, the PCR, 
      Western blot and recovery experiment were used to confirm the function of target 
      gene, mammalian target of rapamycin (mTOR), in vitro. RESULTS: The expression of 
      miR-199a-3p was upregulated in plasma exosomes and diseased colonic tissues of 
      patients with HSCR. In vitro, miR-199a-3p can inhibit cell proliferation and 
      migration. Bioinformatic analysis suggested that mTOR might be a potential target 
      of miR-199a-3p in HSCR. mTOR was discovered to be downregulated by miR-199a-3p in 
      vitro. The negative connection between mTOR and miR-199a-3p was confirmed in 
      tissue samples. mTOR can partially reverse the effect of miR-199a-3p on cell 
      proliferation and migration function in vitro. CONCLUSIONS: miR-199a-3p 
      suppresses cell growth and motility, partially by targeting mTOR. Plasma exosomal 
      miR-199a-3p, a diagnostic marker, is crucial for the development of HSCR.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Daiyue, Yu
AU  - Daiyue Y
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China.
FAU - Zhaorong, Huang
AU  - Zhaorong H
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China.
FAU - Yi, Lu
AU  - Yi L
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China.
FAU - Chen, Wang
AU  - Chen W
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China.
FAU - Caiyun, Luo
AU  - Caiyun L
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China.
FAU - Yuqian, Su
AU  - Yuqian S
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China.
FAU - Liucheng, Yang
AU  - Liucheng Y
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China.
FAU - Kai, Wu
AU  - Kai W
AD  - Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, 510282, Guangdong, China. wukai@smu.edu.cn.
LA  - eng
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
GR  - 2019A1515011086/Guangdong Basic and Applied Basic Research Foundation of China/
PT  - Journal Article
DEP - 20221219
PL  - Germany
TA  - Pediatr Surg Int
JT  - Pediatric surgery international
JID - 8609169
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (mirn199 microRNA, human)
SB  - IM
MH  - Humans
MH  - Cell Proliferation/genetics
MH  - *Hirschsprung Disease/genetics
MH  - *MicroRNAs/genetics
MH  - *TOR Serine-Threonine Kinases/genetics/metabolism
MH  - *Exosomes
OTO - NOTNLM
OT  - Exosomes
OT  - Hirschsprung's disease
OT  - mTOR
OT  - miR-199a-3p
EDAT- 2022/12/20 06:00
MHDA- 2022/12/22 06:00
CRDT- 2022/12/19 11:14
PHST- 2022/12/05 00:00 [accepted]
PHST- 2022/12/19 11:14 [entrez]
PHST- 2022/12/20 06:00 [pubmed]
PHST- 2022/12/22 06:00 [medline]
AID - 10.1007/s00383-022-05337-2 [pii]
AID - 10.1007/s00383-022-05337-2 [doi]
PST - epublish
SO  - Pediatr Surg Int. 2022 Dec 19;39(1):54. doi: 10.1007/s00383-022-05337-2.