PMID- 37507742
OWN - NLM
STAT- MEDLINE
DCOM- 20230814
LR  - 20230814
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 21
IP  - 1
DP  - 2023 Jul 28
TI  - Hsa_circ_0002348 regulates trophoblast proliferation and apoptosis through 
      miR-126-3p/BAK1 axis in preeclampsia.
PG  - 509
LID - 10.1186/s12967-023-04240-1 [doi]
LID - 509
AB  - BACKGROUND: Preeclampsia is a common pregnancy complication characterized by high 
      blood pressure and damage to organs. Abnormal placenta and vascular function can 
      lead to preeclampsia. Accumulating evidence has suggested a potential link 
      between circular RNAs (circRNAs) and preeclampsia. As a placenta and 
      endothelial-expressed circRNA, hsa_circ_0002348, may be promising to be the novel 
      molecular target for preeclampsia. However, the function and mechanism of 
      hsa_circ_0002348 in preeclampsia has not been elucidated. MATERIALS AND METHODS: 
      An overlap analysis of two circRNA profiles from placenta and endothelial cells 
      was used to identify a functionally unknown circRNA, hsa_circ_0002348. 
      Quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH) were used to 
      detect its expression in the trophoblast cells and placental tissues. The mouse 
      model of lipopolysaccharide (LPS)-induced preeclampsia was established to 
      determine the in vivo role of hsa_circ_0002348. RNA immunoprecipitation (RIP), 
      Luciferase reporter assay, qRT-PCR, western blot, gain- and loss-of-function and 
      rescue experiments were conducted to uncover the role of hsa_circ_0002348 and its 
      interaction with miR-126-3p and BAK1 in regulating trophoblast proliferation and 
      apoptosis. Fluorescence in situ hybridization (FISH) and Immunohistochemistry 
      (IHC) were performed to examine the expression of miR-126-3p and BAK1 in mice and 
      human placentas, respectively. RESULTS: Hsa_circ_0002348 was significantly 
      increased in the preeclampsia placentas, and positively correlated with the 
      severity of preeclampsia patients' clinical manifestations. Its overexpression 
      exacerbated preeclampsia-like features in the mouse model of LPS-induced 
      preeclampsia. Functionally, hsa_circ_0002348 was found to inhibit trophoblast 
      proliferation and promote trophoblast apoptosis. Mechanistically, 
      hsa_circ_0002348, as an endogenous miR-126-3p sponge, upregulated the expression 
      of BAK1. Additionally, both hsa_circ_0002348 knockdown and miR-126-3p 
      overexpression enhanced the mammalian target of rapamycin (mTOR) and ERK1/2 
      signaling pathway. CONCLUSIONS: Hsa_circ_0002348 might be a novel regulator of 
      trophoblast proliferation and apoptosis through miR-126-3p/BAK1 axis in 
      preeclampsia, which may serve as a potential target for detecting and treating 
      preeclampsia.
CI  - (c) 2023. The Author(s).
FAU - Zhou, Jizi
AU  - Zhou J
AUID- ORCID: 0000-0001-7527-9534
AD  - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
AD  - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 
      Shanghai, China.
FAU - Zhao, Ying
AU  - Zhao Y
AD  - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
AD  - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 
      Shanghai, China.
FAU - An, Ping
AU  - An P
AD  - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
AD  - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 
      Shanghai, China.
FAU - Zhao, Huanqiang
AU  - Zhao H
AD  - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
AD  - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 
      Shanghai, China.
FAU - Li, Xiaotian
AU  - Li X
AD  - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. 
      xiaotianli555@163.com.
AD  - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 
      Shanghai, China. xiaotianli555@163.com.
AD  - Institute of Biomedical Sciences, Fudan University, Shanghai, China. 
      xiaotianli555@163.com.
FAU - Xiong, Yu
AU  - Xiong Y
AD  - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. 
      xiongyu1535@163.com.
AD  - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 
      Shanghai, China. xiongyu1535@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230728
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (BAK1 protein, human)
RN  - 0 (Bak1 protein, mouse)
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN126 microRNA, human)
RN  - 0 (MIRN126 microRNA, mouse)
RN  - 0 (RNA, Circular)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Mice
MH  - Pregnancy
MH  - Apoptosis/genetics
MH  - bcl-2 Homologous Antagonist-Killer Protein/genetics
MH  - Cell Proliferation/genetics
MH  - Disease Models, Animal
MH  - Endothelial Cells
MH  - In Situ Hybridization, Fluorescence
MH  - Lipopolysaccharides
MH  - Mammals
MH  - *MicroRNAs/genetics
MH  - Placenta
MH  - *Pre-Eclampsia/genetics
MH  - *RNA, Circular/genetics
MH  - Trophoblasts
PMC - PMC10375637
OTO - NOTNLM
OT  - Apoptosis
OT  - CircRNA
OT  - Preeclampsia
OT  - Proliferation
OT  - Trophoblast
OT  - miR-126-3p/BAK1 axis
COIS- The authors declare no conflict of interests.
EDAT- 2023/07/29 06:41
MHDA- 2023/07/31 11:42
PMCR- 2023/07/28
CRDT- 2023/07/28 23:39
PHST- 2022/12/28 00:00 [received]
PHST- 2023/05/31 00:00 [accepted]
PHST- 2023/07/31 11:42 [medline]
PHST- 2023/07/29 06:41 [pubmed]
PHST- 2023/07/28 23:39 [entrez]
PHST- 2023/07/28 00:00 [pmc-release]
AID - 10.1186/s12967-023-04240-1 [pii]
AID - 4240 [pii]
AID - 10.1186/s12967-023-04240-1 [doi]
PST - epublish
SO  - J Transl Med. 2023 Jul 28;21(1):509. doi: 10.1186/s12967-023-04240-1.