PMID- 37300650
OWN - NLM
STAT- MEDLINE
DCOM- 20230719
LR  - 20230720
IS  - 1573-7330 (Electronic)
IS  - 1058-0468 (Print)
IS  - 1058-0468 (Linking)
VI  - 40
IP  - 7
DP  - 2023 Jul
TI  - miR-101-5p suppresses trophoblast cell migration and invasion via modulating the 
      DUSP6-ERK1/2 axis in preeclampsia.
PG  - 1597-1610
LID - 10.1007/s10815-023-02846-4 [doi]
AB  - PURPOSE: Dysregulated behaviors of trophoblast cells leading to defective 
      placentation are considered the main cause of preeclampsia (PE). Abnormal miRNA 
      expression profiles have been observed in PE placental tissue, indicating the 
      significant role of miRNAs in PE development. This study aimed to investigate the 
      expression of miR-101-5p in PE placental tissue and its biological functions. 
      METHODS: The expression of miR-101-5p in placental tissue was detected by 
      quantitative real-time PCR (qRT-PCR). The localization of miR-101-5p in term 
      placental tissue and decidual tissue was determined by the fluorescence in situ 
      hybridization (FISH)-immunofluorescence (IF) double labeling assay. The effect of 
      miR-101-5p on the migration, invasion, proliferation, and apoptosis of the 
      HTR8/SVneo trophoblast cells was investigated. Online databases combined with 
      transcriptomics were used to identify potential target genes and related pathways 
      of miR-101-5p. Finally, the interaction between miR-101-5p and the target gene 
      was verified by qRT-PCT, WB, dual-luciferase reporter assay, and rescue 
      experiments. RESULTS: The study found that miR-101-5p was upregulated in PE 
      placental tissue compared to normal controls and was mainly located in various 
      trophoblast cell subtypes in placental and decidual tissues. Overexpression of 
      miR-101-5p impaired the migration and invasion of HTR8/SVneo cells. DUSP6 was 
      identified as a potential downstream target of miR-101-5p. The expression of 
      miR-101-5p was negatively correlated with DUSP6 expression in HTR8/SVneo cells, 
      and miR-101-5p directly bound to the 3' UTR region of DUSP6. DUSP6 upregulation 
      rescued the migratory and invasive abilities of HTR8/SVneo cells in the presence 
      of miR-101-5p overexpression. Additionally, miR-101-5p downregulated DUSP6, 
      resulting in enhanced ERK1/2 phosphorylation. CONCLUSION: This study revealed 
      that miR-101-5p inhibits the migration and invasion of HTR8/SVneo cells by 
      regulating the DUSP6-ERK1/2 axis, providing a new molecular mechanism for the 
      pathogenesis of PE.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Xu, Jiacheng
AU  - Xu J
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China.
FAU - Wang, Jie
AU  - Wang J
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China.
FAU - Chen, Miaomiao
AU  - Chen M
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
AD  - Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei Province, 
      China.
FAU - Chao, Bingdi
AU  - Chao B
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China.
FAU - He, Jie
AU  - He J
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China.
FAU - Bai, Yuxiang
AU  - Bai Y
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
FAU - Luo, Xiaofang
AU  - Luo X
AD  - Reproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
FAU - Liu, Hongli
AU  - Liu H
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China.
FAU - Xie, Lumei
AU  - Xie L
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China.
FAU - Tao, Yuelan
AU  - Tao Y
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China.
FAU - Qi, Hongbo
AU  - Qi H
AUID- ORCID: 0000-0003-3776-0487
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China. 
      qihongbocy@gmail.com.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China. qihongbocy@gmail.com.
AD  - Women and Children's Hospital of Chongqing Medical University, Chongqing, China. 
      qihongbocy@gmail.com.
FAU - Luo, Xin
AU  - Luo X
AD  - Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China. 
      14802315@qq.com.
AD  - Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical 
      University, Chongqing, China. 14802315@qq.com.
LA  - eng
PT  - Journal Article
DEP - 20230610
PL  - Netherlands
TA  - J Assist Reprod Genet
JT  - Journal of assisted reproduction and genetics
JID - 9206495
RN  - 0 (MicroRNAs)
RN  - EC 3.1.3.48 (DUSP6 protein, human)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 6)
RN  - 0 (MIRN101 microRNA, human)
SB  - IM
MH  - Humans
MH  - Pregnancy
MH  - Female
MH  - Placenta/metabolism
MH  - Trophoblasts/metabolism
MH  - *Pre-Eclampsia/pathology
MH  - In Situ Hybridization, Fluorescence
MH  - MAP Kinase Signaling System/genetics
MH  - Cell Line
MH  - *MicroRNAs/genetics/metabolism
MH  - Cell Proliferation/genetics
MH  - Dual Specificity Phosphatase 6/genetics/metabolism
PMC - PMC10352218
OTO - NOTNLM
OT  - DUSP6
OT  - ERK1/2
OT  - Invasion
OT  - Migration
OT  - Preeclampsia
OT  - miR-101-5p
COIS- The authors declare no competing interests.
EDAT- 2023/06/10 23:42
MHDA- 2023/07/19 06:43
PMCR- 2024/07/01
CRDT- 2023/06/10 11:08
PHST- 2023/04/27 00:00 [received]
PHST- 2023/05/31 00:00 [accepted]
PHST- 2024/07/01 00:00 [pmc-release]
PHST- 2023/07/19 06:43 [medline]
PHST- 2023/06/10 23:42 [pubmed]
PHST- 2023/06/10 11:08 [entrez]
AID - 10.1007/s10815-023-02846-4 [pii]
AID - 2846 [pii]
AID - 10.1007/s10815-023-02846-4 [doi]
PST - ppublish
SO  - J Assist Reprod Genet. 2023 Jul;40(7):1597-1610. doi: 10.1007/s10815-023-02846-4. 
      Epub 2023 Jun 10.