The lncRNA DANCR promotes development of atherosclerosis by regulating the miR-214-5p/COX20 signaling pathway.
Cell Mol Biol Lett
; 27(1): 15, 2022 Feb 17.
Article
en En
| MEDLINE
| ID: mdl-35177003
ABSTRACT
BACKGROUND:
Although long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) has been reported to be involved in atherosclerosis (AS) development, its specific mechanism remains unclear.METHODS:
DANCR expression levels in blood samples of AS patients and oxidized low-density lipoprotein (ox-LDL) treated vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The small interfering RNA targeting DANCR (si-DANCR) was used to silence DANCR expression. Cell viability was assessed by CCK-8 assay. Cell apoptosis was evaluated by flow cytometry. Levels of inflammatory cytokines, anti-oxidative enzyme superoxide dismutase (SOD) activity, and malonaldehyde (MDA) were detected by specific commercial kits. An animal AS model was established to confirm the role of DANCR/microR-214-5p/COX20 (the chaperone of cytochrome c oxidase subunit II COX2) in AS development.RESULTS:
DANCR was significantly increased in the blood samples of AS patients and ox-LDL treated VSMCs and HUVECs. DANCR downregulation obviously increased viability and reduced apoptosis of ox-LDL-treated VSMCs and HUVECs. Meanwhile, DANCR downregulation reduced the levels of inflammatory cytokines, including interleukin (IL)-6 (IL-6), IL-1beta (IL-1ß), IL-6 and tumor necrosis factor (TNF)-alpha (TNF-α) and MDA while increasing the SOD level in ox-LDL-treated VSMCs and HUVECs. DANCR regulated COX20 expression by acting as a competing endogenous RNA (ceRNA) of miR-214-5p. Rescue experiments demonstrated that miR-214-5p downregulation obviously attenuated si-DANCR-induced protective effects on ox-LDL-caused endothelial injury.CONCLUSIONS:
Our results revealed that DANCR promoted AS progression by targeting the miR-214-5p/COX20 axis, suggesting that DANCR might be a potential therapeutic target for AS.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Aterosclerosis
/
ARN Largo no Codificante
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Mol Biol Lett
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2022
Tipo del documento:
Article