lncRNA NEAT1 Downregulation Ameliorates the Myocardial Infarction of Mice by Regulating the miR-582-5p/F2RL2 Axis.

This study is aimed at effectively investigating the role of coagulation factor II thrombin receptor like 2 (F2RL2) in myocardial infarction (MI) as well as the upstream regulatory miRNA and lncRNA. Regulatory genes of F2RL2 were analyzed using StarBase and verified by dual-luciferase reporter assay. The MI mouse model was established. The left ventricular ejection fraction (EF) and fractional shortening (FS) were examined by echocardiography. The infarct area, pathological changes, and cell apoptosis in mouse myocardial tissue were evaluated using triphenyltetrazolium chloride and Evans blue, hematoxylin-eosin, and TUNEL staining assays. Oxygen-glucose deprivation- (OGD-) induced human cardiac myocytes (HCMs) were cultured and transfected. The cell viability, proliferation, and apoptosis were determined by CCK-8, EdU staining, and flow cytometry assays. The expressions of F2RL2, miR-582-5p, and nuclear paraspeckle assembly transcript 1 (NEAT1) in myocardial tissues and HCMs were quantified by qRT-PCR or Western blot. NEAT1 sponged miR-582-5p which targeted F2RL2. NEAT1 and F2RL2 were highly expressed while miR-582-5p was lowly expressed in MI mice. F2RL2 downregulation prevented the reduction in EF and SF and the elevation in infarct area and cell apoptosis of MI mice. Both F2RL2 and NEAT1 downregulations reversely modulated the decreased viability and proliferation and the increased apoptosis of OGD-induced HCMs, while miR-582-5p inhibitor did oppositely. NEAT1 silencing upregulated miR-582-5p level but downregulated F2RL2 level. miR-582-5p inhibitor upregulated the F2RL2 level. The role of NEAT1 silencing in OGD-induced HCMs was reversed by miR-582-5p inhibitor whose effect was further offset by F2RL2 downregulation. NEAT1 downregulation ameliorates MI by regulating the miR-582-5p/F2RL2 axis, providing novel biomarkers for MI treatment.

Wu Z ，Bai Y ，Qi Y ，Chang C ，Jiao Y ，Bai Y ，Guo Z ... -  《-》

Down-regulating NEAT1 inhibited the viability and vasculogenic mimicry formation of sinonasal squamous cell carcinoma cells via miR-195-5p/VEGFA axis.

The role of long non-coding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) in sinonasal squamous cell carcinoma (SNSCC) remained obscure. Target genes and potential binding sites of NEAT1, microRNA (miR)-195-5p and VEGFA were predicted using StarBase and TargetScan, and confirmed by dual-luciferase reporter assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of NEAT1, vascular endothelial growth factor A (VEGFA) and miR-195-5p. Pearson's correlation analysis of NEAT1, miR-195-5p and VEGFA was conducted. Cell viability, apoptosis and tube formation capability were assessed by MTT assay, flow cytometry and capillary-like tube formation assay, respectively. Expressions of VEGFA and proteins related to the phosphatidylinositide 3-kinase/Protein Kinase B (PI3K/AKT) pathway were measured by Western blot. In SNSCC tissues and cells, the expressions of NEAT1 and VEGFA were up-regulated while the expression of miR-195-5p was down-regulated, and NEAT1 was negatively correlated with miR-195-5p yet positively correlated with VEGFA. Overexpressed VEGFA promoted the viability and capillary-like tube formation of SNSCC cells yet suppressed their apoptosis, while silencing VEGFA led to the opposite results. MiR-195-5p could bind to NEAT1, and down-regulating miR-195-5p reversed the effects of silencing NEAT1 on the expressions of NEAT1 and miR-195-5p, cell viability, apoptosis and capillary-like tube formation as well as PI3K/AKT pathway activation. VEGFA was the target of miR-195-5p, and overexpressed VEGFA reversed the effects of miR-195-5p. Down-regulating NEAT1 inhibited the viability and vasculogenic mimicry formation of SNSCC cells yet promoted their apoptosis via the miR-195-5p/VEGFA axis, providing a possible therapeutic target for SNSCC treatment.

Lu H ，Kang F 《-》

Long Noncoding RNA NEAT1 Promotes the Progression of Breast Cancer by Regulating miR-138-5p/ZFX Axis.

Yao L ，Chen L ，Zhou H ，Duan F ，Wang L ，Zhang Y ... -  《-》

miR-125b-5p alleviates the damage of myocardial infarction by inhibiting the NFAT2 to reduce F2RL2 expression.

Wu Z ，Geng J ，Bai Y ，Qi Y ，Chang C ，Jiao Y ，Guo Z ... -  《-》

LncRNA NEAT1 knockdown ameliorates LPS-induced human kidney injury by mediating the miR-330-5p/FOXO3 axis.

Sepsis is a systemic process with multiple inflammatory responses and organ injuries, particularly in the damage of the kidney. Recently, numerous studies suggest that long non-coding RNAs (lncRNAs) are involved in sepsis-related kidney injury. This study aimed to investigate the functional role and mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in sepsis-related kidney injury. Cell model of kidney injury was constructed in human kidney 2 (HK-2) cells with the treatment of lipopolysaccharide (LPS). The expression of NEAT1 was measured by quantitative real-time PCR (qRT-PCR). Cell viability was examined using CCK-8 assay. Flow cytometry was performed to detect cell apoptosis, and apoptosis-related proteins were quantified by western blot. The release of proinflammatory cytokines was assessed by ELISA. Oxidative stress was assessed by the levels of SOD and MDA using kits. The putative relationship between miR-330-5p and NEAT1 or FOXO3 was confirmed using dual-luciferase reporter assay, RIP assay and pull-down assay. The expression of NEAT1 was increased in LPS-treated HK-2 cells. LPS exposure promoted apoptotic rate, inflammatory responses and oxidative stress in HK-2 cells, which were largely ameliorated by NEAT1 knockdown. MiR-330-5p was verified as a target of NEAT1, and miR-330-5p inhibition reversed the effects of NEAT1 knockdown in LPS-treated HK-2 cells. Moreover, FOXO3 was a target of miR-330-5p, and miR-330-5p restoration-blocked cell apoptosis, inflammation and oxidative stress in LPS-treated HK-2 cells were recovered by FOXO3 overexpression. NEAT1 downregulation meliorated LPS-induced HK-2 cell injuries partly by regulating the miR-330-5p/FOXO3 pathway.

Gong Y ，Dong X ，Xu J ，Yang W ... -  《-》