PMID- 36241224
OWN - NLM
STAT- MEDLINE
DCOM- 20230626
LR  - 20230821
IS  - 2059-8696 (Electronic)
IS  - 2059-8688 (Print)
IS  - 2059-8688 (Linking)
VI  - 8
IP  - 3
DP  - 2023 Jun
TI  - MALAT1 promotes platelet activity and thrombus formation through PI3k/Akt/GSK-3beta 
      signalling pathway.
PG  - 181-192
LID - 10.1136/svn-2022-001498 [doi]
AB  - BACKGROUND: Ischaemic stroke and other cardiovascular illnesses are characterised 
      by abnormalities in the processes of thrombosis and haemostasis, which rely on 
      platelet activity. In platelets, a wide variety of microRNAs (long non-coding 
      RNA, lncRNAs) is found. Due to the absence of nuclear DNA in platelets, lncRNAs 
      may serve as critical post-transcriptional regulators of platelet activities. 
      However, research into the roles of lncRNAs in platelets is limited. OBJECTIVE: 
      The purpose of this study is to learn more about the molecular mechanism by which 
      MALAT1 affects platelet activity and thrombus formation. METHODS/RESULTS: The 
      CD34(+) megakaryocytes used in this research as an in vitro model for human 
      megakaryocytes and platelets. Cell adhesion and spreading are enhanced in the 
      absence and presence of agonists in CD34(+) megakaryocytes subjected to MALAT1 
      knockdown (KD). The adhesion and activity of platelet-like particles produced by 
      MALAT1 KD cells are significantly enhanced at rest and after thrombin activation. 
      Thrombus development on a collagen matrix is also greatly enhanced in the 
      microfluidic whole-blood perfusion model: platelets lacking MALAT1 exhibit 
      elevated accumulation, distributing area and activity. In addition, 
      MALAT1-deficient mice bleed less and form a stable occlusive thrombus more 
      quickly than wild-type mice. PTEN and PDK1 regulated the activity of MALAT1 in 
      platelets to carry out its PI3k/Akt/GSK-3beta signalling pathway-related function. 
      CONCLUSION: The suppression of MALAT1 expression significantly increases platelet 
      adhesion, spreading, platelet activity, and thrombus formation. lncRNAs may 
      constitute a unique class of platelet function modulators.
CI  - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Sun, Yeying
AU  - Sun Y
AUID- ORCID: 0000-0003-0397-1083
AD  - College of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
FAU - Wang, Tao
AU  - Wang T
AD  - College of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
FAU - Lv, Yan
AU  - Lv Y
AD  - College of Life Sciences, Yantai University, Yantai, Shandong, China.
FAU - Li, Jiahua
AU  - Li J
AD  - College of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
FAU - Jiang, Xiaoli
AU  - Jiang X
AD  - College of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
FAU - Jiang, Jing
AU  - Jiang J
AD  - College of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
FAU - Zhang, Daolai
AU  - Zhang D
AD  - College of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
FAU - Bian, Weihua
AU  - Bian W
AUID- ORCID: 0000-0003-2369-2073
AD  - College of Pharmacy, Binzhou Medical University, Yantai, Shandong, China 
      bzmczcx@163.com bian_1005@163.com.
FAU - Zhang, Chunxiang
AU  - Zhang C
AD  - College of Pharmacy, Binzhou Medical University, Yantai, Shandong, China 
      bzmczcx@163.com bian_1005@163.com.
AD  - Department of Cardiology, Southwest Medical University, Luzhou, Sichuan, China.
LA  - eng
PT  - Journal Article
DEP - 20221014
PL  - England
TA  - Stroke Vasc Neurol
JT  - Stroke and vascular neurology
JID - 101689996
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - 0 (RNA, Long Noncoding)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Blood Platelets/metabolism
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - *RNA, Long Noncoding/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Platelet Aggregation
MH  - *Brain Ischemia/metabolism
MH  - Disease Models, Animal
MH  - *Stroke/metabolism
MH  - *Thrombosis/genetics
PMC - PMC10359792
OTO - NOTNLM
OT  - Blood Platelets
OT  - Thromboembolism
COIS- Competing interests: None declared.
EDAT- 2022/10/15 06:00
MHDA- 2023/06/26 06:42
PMCR- 2022/10/14
CRDT- 2022/10/14 20:53
PHST- 2022/01/11 00:00 [received]
PHST- 2022/09/21 00:00 [accepted]
PHST- 2023/06/26 06:42 [medline]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2022/10/14 20:53 [entrez]
PHST- 2022/10/14 00:00 [pmc-release]
AID - svn-2022-001498 [pii]
AID - 10.1136/svn-2022-001498 [doi]
PST - ppublish
SO  - Stroke Vasc Neurol. 2023 Jun;8(3):181-192. doi: 10.1136/svn-2022-001498. Epub 
      2022 Oct 14.