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 (HIF1α) 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 HIF1α/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 'HIF1α/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.