PMID- 34790800
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220428
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 20
DP  - 2021 Oct
TI  - MiR-139-5p has an antidepressant-like effect by targeting phosphodiesterase 4D to 
      activate the cAMP/PKA/CREB signaling pathway.
PG  - 1594
LID - 10.21037/atm-21-5149 [doi]
LID - 1594
AB  - BACKGROUND: Phosphodiesterase 4D (PDE4D) inhibitor is commonly used to treat 
      depression, but side effects seriously decrease its efficacy. PDE4D was a 
      downstream target mRNA of miR-139-5p. Therefore, we examined the effects of 
      hippocampal miR-139-5p gain- and loss-of-function on depression-like behaviors, 
      the expression level of PDE4D, and hippocampus neurogenesis. METHODS: 
      Bioinformatic analyses were carried out to to screen differential genes. 
      Quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase 
      reporter assay were used to confirm the relationship between miR-139-5p and 
      PDE4D. MiR-139-5p mimics, miR-139-5p inhibitor, or miR-NC were used to explore 
      the function of miR-139-5p in HT-22 cells. We further explored the role of 
      miR-139-5p in vivo using AAV-injection. Elisa, western blotting, and fluorescence 
      in situ hybridization (FISH) were used to detect the expression of miR-139-5p and 
      PDE4D in CRC tissues. RESULTS: Here, we showed that PDE4D messenger RNA (mRNA) 
      was a direct target of microRNA (miR)-139-5p, which was downregulated in a 
      chronic ultra-mild stress (CUMS)-induced depression mouse model. Moreover, in 
      experiments in vitro, miR-139-5p mimic repressed PDE4D expression in HT-22 cells, 
      but promoted phosphorylated cyclic-AMP response element-binding protein (p-CREB) 
      and brain-derived neurotrophic factor (BDNF) expression. Interestingly, 
      adeno-associated virus (AAV)-miR-139-5p downregulated susceptibility to 
      stress-induced depression-like behaviors in mice. AAV-miR-139-5p suppressed PDE4D 
      in mouse hippocampal cells, increasing expression level of cyclic adenosine 
      monophosphate (cAMP), p-CREB, and BDNF, and stimulating mouse hippocampal 
      neurogenesis. CONCLUSIONS: Our findings suggested that miR-139-5p acted like an 
      antidepressant by targeting PDE4D, thereby regulating the cAMP/protein kinase A 
      (PKA)/CREB/BDNF pathway to improve depression.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Huang, Peng
AU  - Huang P
AD  - South Medical University Affiliated Maternal & Child Health Hospital of Foshan, 
      Foshan, China.
FAU - Wei, Songren
AU  - Wei S
AD  - Department of Neuropharmacology and Novel Drug Discovery, School of 
      Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
FAU - Luo, Meng
AU  - Luo M
AD  - Center for Bioinformatics, School of Life Science and Technology, Harbin 
      Institute of Technology, Harbin, China.
FAU - Tang, Zhuohong
AU  - Tang Z
AD  - South Medical University Affiliated Maternal & Child Health Hospital of Foshan, 
      Foshan, China.
FAU - Lin, Qingmei
AU  - Lin Q
AD  - South Medical University Affiliated Maternal & Child Health Hospital of Foshan, 
      Foshan, China.
FAU - Wang, Xing
AU  - Wang X
AD  - South Medical University Affiliated Maternal & Child Health Hospital of Foshan, 
      Foshan, China.
FAU - Luo, Mi
AU  - Luo M
AD  - South Medical University Affiliated Maternal & Child Health Hospital of Foshan, 
      Foshan, China.
FAU - He, Yanjun
AU  - He Y
AD  - South Medical University Affiliated Maternal & Child Health Hospital of Foshan, 
      Foshan, China.
FAU - Wang, Chuan
AU  - Wang C
AD  - Department of Biliary Surgery, The First People's Hospital of Foshan, Foshan, 
      China.
FAU - Wei, Dezhan
AU  - Wei D
AD  - South Medical University Affiliated Maternal & Child Health Hospital of Foshan, 
      Foshan, China.
FAU - Xia, Chenglai
AU  - Xia C
AD  - South Medical University Affiliated Maternal & Child Health Hospital of Foshan, 
      Foshan, China.
AD  - School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
FAU - Xu, Jiangping
AU  - Xu J
AD  - Department of Neuropharmacology and Novel Drug Discovery, School of 
      Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8576692
OTO - NOTNLM
OT  - Depression
OT  - brain-derived neurotrophic factor (BDNF)
OT  - cyclic adenosine monophosphate (cAMP)
OT  - miR-139-5p
OT  - phosphodiesterase 4D (PDE4D)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/atm-21-5149). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/11/19 06:00
MHDA- 2021/11/19 06:01
PMCR- 2021/10/01
CRDT- 2021/11/18 07:02
PHST- 2021/08/31 00:00 [received]
PHST- 2021/10/22 00:00 [accepted]
PHST- 2021/11/18 07:02 [entrez]
PHST- 2021/11/19 06:00 [pubmed]
PHST- 2021/11/19 06:01 [medline]
PHST- 2021/10/01 00:00 [pmc-release]
AID - atm-09-20-1594 [pii]
AID - 10.21037/atm-21-5149 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Oct;9(20):1594. doi: 10.21037/atm-21-5149.