PMID- 34803510
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211223
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 17
IP  - 15
DP  - 2021
TI  - miRNA-223 Suppresses Mouse Gallstone Formation by Targeting Key Transporters in 
      Hepatobiliary Cholesterol Secretion Pathway.
PG  - 4459-4473
LID - 10.7150/ijbs.65485 [doi]
AB  - miRNA-223 has been previously reported to play an essential role in hepatic 
      cholesterol homeostasis. However, its role in regulation of biliary cholesterol 
      secretion and gallstone formation remains unknown. Hence, mice with conventional 
      knockout (KO), hepatocyte-specific knockout (DeltaHepa) / knockdown (KD) or gain 
      expression of miRNA-223 were included in the study and were subjected to 
      lithogenic diet (LD) for various weeks. The gall bladders and liver tissues were 
      harvested for cholesterol crystal imaging, gallstone mass measurement and 
      molecular analysis. Levels of cholesterol, bile salt, phospholipids, and 
      triglyceride were determined in serum, liver tissues, and bile by enzyme color 
      reactive assays. A 3' UTR reporter gene assay was used to verify the direct 
      target genes for miRNA-223. LD-induced gallstone formation was remarkably 
      accelerated in miRNA-223 KO, DeltaHepa, and KD mice with concurrent enhancement in 
      total cholesterol levels in liver tissues and bile. Key biliary cholesterol 
      transporters ABCG5 and ABCG8 were identified as direct targets of miRNA-223. 
      Reversely, AAV-mediated hepatocyte-specific miRNA-223 overexpression prevented 
      gallstone progression with reduced targets expression. Therefore, the present 
      study demonstrates a novel role of miRNA-223 in the gallstone formation by 
      targeting ABCG5 and ABCG8 and elevating miRNA-223 would be a potentially novel 
      approach to overcome the sternness of cholesterol gallstone disease.
CI  - (c) The author(s).
FAU - Zhao, Feng
AU  - Zhao F
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Ma, Shiyu
AU  - Ma S
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Zhou, Yuling
AU  - Zhou Y
AD  - Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, 361004, China.
FAU - Wei, Bailing
AU  - Wei B
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Hao, Zhen
AU  - Hao Z
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Cui, Xiaolin
AU  - Cui X
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Xing, Lina
AU  - Xing L
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Liu, Gang
AU  - Liu G
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Jin, Lingling
AU  - Jin L
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Ma, Tonghui
AU  - Ma T
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
FAU - Shi, Lei
AU  - Shi L
AD  - College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section 
      Lvshun South Road, Dalian 116044, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211025
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (MIRN223 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cholesterol/*metabolism
MH  - Gallbladder/*metabolism
MH  - Gallstones/genetics/metabolism/*prevention & control
MH  - Gene Expression Regulation
MH  - HEK293 Cells
MH  - Hepatocytes/metabolism
MH  - Humans
MH  - Liver/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - MicroRNAs/genetics/*metabolism
PMC - PMC8579439
OTO - NOTNLM
OT  - ABCG5 and ABCG8
OT  - gallstone
OT  - miRNA-223
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2021/11/23 06:00
MHDA- 2021/12/21 06:00
PMCR- 2021/01/01
CRDT- 2021/11/22 06:37
PHST- 2021/07/29 00:00 [received]
PHST- 2021/10/08 00:00 [accepted]
PHST- 2021/11/22 06:37 [entrez]
PHST- 2021/11/23 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - ijbsv17p4459 [pii]
AID - 10.7150/ijbs.65485 [doi]
PST - epublish
SO  - Int J Biol Sci. 2021 Oct 25;17(15):4459-4473. doi: 10.7150/ijbs.65485. 
      eCollection 2021.