PMID- 35638109
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220716
IS  - 1555-8584 (Electronic)
IS  - 1547-6286 (Print)
IS  - 1547-6286 (Linking)
VI  - 19
IP  - 1
DP  - 2022 Jan
TI  - DARS-AS1 recruits METTL3/METTL14 to bind and enhance DARS mRNA m(6)A modification 
      and translation for cytoprotective autophagy in cervical cancer.
PG  - 751-763
LID - 10.1080/15476286.2022.2079889 [doi]
AB  - Cervical cancer (CC) is one of the most prevalent malignancies among females. 
      Cytoprotective autophagy could confer cancer cell tolerance to hypoxic stress, 
      promoting cell survival and adaptation. Aspartyl-tRNA synthetase 1 antisense 1 
      (DARS-AS1) is an oncogenic long non-coding RNA (lncRNA) in various cancers, but 
      how DARS-AS1 regulates cytoprotective autophagy in hypoxic environment in CC 
      remains unclear. Chromatin immunoprecipitation (ChIP) and luciferase reporter 
      assays were conducted to explore the interaction between hypoxia-inducible factor 
      1 subunit alpha (HIF1alpha) and DARS-AS1 promoter. Methylated RNA immunoprecipitation 
      (MeRIP) followed by quantitative real-time polymerase-chain reaction (RT-qPCR) 
      detected methylated RNA level. The process of autophagic maturation was monitored 
      by immunofluorescence staining. Higher DARS-AS1 expression was found in CC 
      tissues and cytoprotective. We also uncovered that hypoxic exposure induced 
      cytoprotective autophagy via HIF1alpha/DARS-AS1/DARS axis. Moreover, DARS-AS1 was 
      validated to facilitate DARS translation via recruiting 
      N6-adenosine-methyltransferase methyltransferase like 3 (METTL3) and 
      methyltransferase like 14 (METTL14), which bound with DARS mRNA DARS mRNA 5' 
      untranslated region (5'UTR) and promoting its translation. The present study 
      demonstrated that the 'HIF1alpha/DARS-AS1/DARS/ATG5/ATG3' pathway regulated the 
      hypoxia-induced cytoprotective autophagy of CC and might be a promising target of 
      therapeutic strategies for patients afflicted with CC.
FAU - Shen, Weiwei
AU  - Shen W
AD  - Department of Gynecology, The Affiliated Hospital of Medical School, Ningbo 
      University, Ningbo, Zhejiang, China.
FAU - Zhu, Miaohua
AU  - Zhu M
AD  - Department of Gynecology, Ningbo Women's & Children's Hospital, Ningbo 
      University, Ningbo, Zhejiang, China.
FAU - Wang, Qiming
AU  - Wang Q
AD  - Department of Gynecology, Ningbo Women's & Children's Hospital, Ningbo 
      University, Ningbo, Zhejiang, China.
FAU - Zhou, Xiaoming
AU  - Zhou X
AD  - Department of Gynecology, The Affiliated Hospital of Medical School, Ningbo 
      University, Ningbo, Zhejiang, China.
FAU - Wang, Jiaying
AU  - Wang J
AD  - Department of Gynecology, The Affiliated Hospital of Medical School, Ningbo 
      University, Ningbo, Zhejiang, China.
FAU - Wang, Tingting
AU  - Wang T
AD  - Department of Gynecology, The Affiliated Hospital of Medical School, Ningbo 
      University, Ningbo, Zhejiang, China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Department of Gynecology, Ningbo Women's & Children's Hospital, Ningbo 
      University, Ningbo, Zhejiang, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - RNA Biol
JT  - RNA biology
JID - 101235328
RN  - 0 (RNA, Antisense)
RN  - 0 (RNA, Messenger)
RN  - EC 2.1.1.- (METTL14 protein, human)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.62 (METTL3 protein, human)
SB  - IM
MH  - *Autophagy/genetics
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - *Methyltransferases/genetics
MH  - RNA, Antisense
MH  - RNA, Messenger/genetics
MH  - *Uterine Cervical Neoplasms/genetics
PMC - PMC9176263
OTO - NOTNLM
OT  - DARS-AS1
OT  - autophagy
OT  - cervical cancer
OT  - m6A modification
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/06/01 06:00
MHDA- 2022/06/03 06:00
PMCR- 2022/05/30
CRDT- 2022/05/31 14:28
PHST- 2022/05/31 14:28 [entrez]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2022/05/30 00:00 [pmc-release]
AID - 2079889 [pii]
AID - 10.1080/15476286.2022.2079889 [doi]
PST - ppublish
SO  - RNA Biol. 2022 Jan;19(1):751-763. doi: 10.1080/15476286.2022.2079889.