PMID- 33402817
OWN - NLM
STAT- MEDLINE
DCOM- 20210921
LR  - 20220419
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 14
DP  - 2020
TI  - Silencing of circHIPK3 Inhibits Pressure Overload-Induced Cardiac Hypertrophy and 
      Dysfunction by Sponging miR-185-3p.
PG  - 5699-5710
LID - 10.2147/DDDT.S245199 [doi]
AB  - BACKGROUND: Cardiac hypertrophy is induced by diverse patho-physiological stimuli 
      and indicates an increase in cardiomyocyte size. Circular RNAs (circRNAs) and 
      microRNAs (miRNAs), members of noncoding RNAs, are involved in several biological 
      processes and cardiovascular diseases (CVD). Here, we investigated the potential 
      role of circHIPK3, which is produced by the third exon of the HIPK3 gene in 
      cardiac hypertrophy. METHODS: qRT-PCR and Sanger sequencing were conducted to 
      identify the expression and characteristics (head-to-tail structure, stability, 
      and location) of circHIPK3 in cardiac hypertrophy; Immunostaining of alpha-SMA was 
      performed to evaluate the size of the cardiomyocytes; Transverse aortic 
      constriction (TAC) induced hypertrophy models of mice were established to 
      investigate the effect of circHIPK3 in vivo. Bioinformatics analysis and 
      luciferase reporter assays, RNA immunoprecipitation, and fluorescence in situ 
      hybridization (FISH) experiments were conducted to investigate the mechanism of 
      circHIPK3-mediated cardiac hypertrophy. RESULTS: circHIPK3 is circular, more 
      stable, and mainly located in the cytoplasm. Silencing of circHIPK3 inhibited the 
      TAC induced cardiac hypertrophy, and reversed the effect of TAC on the 
      echocardiograph parameters, such as left ventricular end-diastolic pressure 
      (LVEDPS), left ventricular fraction shortening (LVFS), left ventricular ejection 
      fraction (LVEF), and left ventricular systolic dysfunction (LVSD), and also the 
      heart weight to tibial length (HW/TL). Angiotensin II (Ang II) Ang II-treated 
      cardiomyocytes showed larger size of cardiomyocyte and upregulation of fetal 
      genes, biomarkers of cardiac hypertrophy, peptide hormones, atrial natriuretic 
      peptide (ANP) and brain natriuretic peptide (BNP), and myofilament protein, 
      beta-myosin heavy chain (beta-MHC). These effects were reversed by circHIPK3 knockdown. 
      Mechanically, circHIPK3 sponges miR-185-3p. In addition, miR-185-3p targets CASR. 
      The rescue experiments confirmed the interaction between circHIPK3 and miR-185-3p 
      as well as miR-185-3p and CASR. DISCUSSION: Our data suggested that circHIPK3 
      serve as a miR-185-3p sponge to regulate cardiac hypertrophy revealing a 
      potential new target for the prevention of TAC- and Ang-II induced cardiac 
      hypertrophy.
CI  - (c) 2020 Xu et al.
FAU - Xu, Xiaohan
AU  - Xu X
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital with Nanjing 
      Medical University, Nanjing 210029, People's Republic of China.
FAU - Wang, Junhong
AU  - Wang J
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital with Nanjing 
      Medical University, Nanjing 210029, People's Republic of China.
FAU - Wang, Xiaowei
AU  - Wang X
AD  - Department of Cardiovascular Surgery, The First Affiliated Hospital with Nanjing 
      Medical University, Nanjing 210029, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20201229
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - EC 2.7.11.1 (Hipk3 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cardiomegaly/*metabolism
MH  - Gene Silencing
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/genetics/*metabolism
MH  - Pressure
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
MH  - RNA, Circular/*genetics/metabolism
PMC - PMC7778681
OTO - NOTNLM
OT  - TAC
OT  - angiotensin II
OT  - calcium signaling receptor
OT  - cardiac hypertrophy
OT  - circHIPK3
OT  - miR-185-3p
OT  - transverse aortic constriction
COIS- The authors report no conflicts of interest in this work.
EDAT- 2021/01/07 06:00
MHDA- 2021/09/22 06:00
PMCR- 2020/12/29
CRDT- 2021/01/06 05:52
PHST- 2020/01/08 00:00 [received]
PHST- 2020/10/18 00:00 [accepted]
PHST- 2021/01/06 05:52 [entrez]
PHST- 2021/01/07 06:00 [pubmed]
PHST- 2021/09/22 06:00 [medline]
PHST- 2020/12/29 00:00 [pmc-release]
AID - 245199 [pii]
AID - 10.2147/DDDT.S245199 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2020 Dec 29;14:5699-5710. doi: 10.2147/DDDT.S245199. 
      eCollection 2020.