PMID- 38242315
OWN - NLM
STAT- MEDLINE
DCOM- 20240423
LR  - 20240423
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 144
IP  - 5
DP  - 2024 May
TI  - N6-Methyladenosine Modification of lncCCKAR-5 Regulates Autophagy in Human 
      Umbilical Cord Mesenchymal Stem Cells by Destabilizing LMNA and Inhibits Diabetic 
      Wound Healing.
PG  - 1148-1160.e15
LID - S0022-202X(23)03216-5 [pii]
LID - 10.1016/j.jid.2023.11.023 [doi]
AB  - Long noncoding RNAs are pivotal contributors to the development of human 
      diseases. However, their significance in the context of diabetic wound healing 
      regulated by human umbilical cord mesenchymal stem cells (hUCMSCs) remains 
      unclear. This study sheds light on the involvement of lncCCKAR5 in this process. 
      We found that hUCMSCs exposed to high glucose conditions exhibited a significant 
      downregulation of lncCCKAR5 expression, and lncCCKAR5 played a critical role in 
      modulating autophagy, thus inhibiting apoptosis in hUCMSCs. In addition, the 
      reduction of lncCCKAR5 in cells exposed to high glucose effectively thwarted 
      cellular senescence and facilitated filopodium formation. Mechanistically, 
      lncCCKAR5 served as a scaffold that facilitated the interaction between MKRN2 and 
      LMNA, a key regulator of cytoskeletal function and autophagy. The 
      lncCCKAR5/LMNA/MKRN2 complex played a pivotal role in promoting the 
      ubiquitin-mediated degradation of LMNA, with this effect being further augmented 
      by N6-adenosine methylation of lncCCKAR5. Consequently, our findings underscore 
      the critical role of lncCCKAR5 in regulating the autophagic process in hUCMSCs, 
      particularly through protein ubiquitination and degradation. This intricate 
      regulatory network presents a promising avenue for potential therapeutic 
      interventions in the context of diabetic wound healing involving hUCMSCs.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Wang, Jian
AU  - Wang J
AD  - Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, China.
FAU - Wang, Xiaotian
AU  - Wang X
AD  - Xuzhou Medical University, Xuzhou, China.
FAU - Chen, Feifei
AU  - Chen F
AD  - Institute of Oncology, Xuzhou Medical University, Xuzhou, China.
FAU - Ning, Qianqian
AU  - Ning Q
AD  - Institute of Oncology, Xuzhou Medical University, Xuzhou, China.
FAU - Liu, YuTing
AU  - Liu Y
AD  - Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, China.
FAU - Zhu, Yun
AU  - Zhu Y
AD  - Xuzhou Medical University, Xuzhou, China.
FAU - Wei, Wuhan
AU  - Wei W
AD  - Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, China.
FAU - Leng, Mengqi
AU  - Leng M
AD  - Xuzhou Medical University, Xuzhou, China.
FAU - Wang, Ziyi
AU  - Wang Z
AD  - Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, China.
FAU - Jin, Peisheng
AU  - Jin P
AD  - Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, China. Electronic address: 100000401006@xzhmu.edu.cn.
FAU - Li, Qiang
AU  - Li Q
AD  - Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, China. Electronic address: liq@xzhmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240117
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - K72T3FS567 (Adenosine)
RN  - 0 (RNA, Long Noncoding)
RN  - CLE6G00625 (N-methyladenosine)
RN  - 0 (Lamin Type A)
RN  - 0 (LMNA protein, human)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Humans
MH  - *Autophagy/drug effects
MH  - *Adenosine/*analogs & derivatives/metabolism
MH  - *Mesenchymal Stem Cells/metabolism/drug effects
MH  - *Wound Healing/drug effects
MH  - *Umbilical Cord/cytology
MH  - *RNA, Long Noncoding/metabolism/genetics
MH  - *Lamin Type A/metabolism/genetics
MH  - Mice
MH  - Cells, Cultured
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Glucose/metabolism/pharmacology
MH  - Cellular Senescence/drug effects
OTO - NOTNLM
OT  - Cell senescence
OT  - Diabetic wound
OT  - Filopodia
OT  - Human umbilical cord mesenchymal stem cells (hUCMSCs)
OT  - Ubiquitination
EDAT- 2024/01/20 05:42
MHDA- 2024/04/23 15:49
CRDT- 2024/01/19 19:16
PHST- 2023/07/12 00:00 [received]
PHST- 2023/10/24 00:00 [revised]
PHST- 2023/11/09 00:00 [accepted]
PHST- 2024/04/23 15:49 [medline]
PHST- 2024/01/20 05:42 [pubmed]
PHST- 2024/01/19 19:16 [entrez]
AID - S0022-202X(23)03216-5 [pii]
AID - 10.1016/j.jid.2023.11.023 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2024 May;144(5):1148-1160.e15. doi: 10.1016/j.jid.2023.11.023. 
      Epub 2024 Jan 17.