Long Noncoding RNA TUG1 Promotes the Function in ox-LDL-Treated HA-VSMCs via miR-141-3p/ROR2 Axis.

Atherosclerosis (AS) is a common severe disease around the world. The merging paper reported that long noncoding RNAs (lncRNAs) took part in diversified pathological processes of AS, although the mechanism remains unknown. This study is aimed at uncovering the profile of lncRNA taurine-upregulated gene 1 (TUG1), which has biological function, and potential mechanism in AS progression in vitro. Oxidized low-density lipoprotein (ox-LDL) was used for AS model construction in vitro. Levels of lncRNA TUG1, miR-141-3p, and receptor tyrosine kinase-like orphan receptor 2 (ROR2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in AS tissues or in ox-LDL-treated vascular smooth muscle cells (HA-VSMCs). The biofunctional effects were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and transwell assays. The expression of proliferation-related proteins (CyclinD1, Ki-67) and metastasis-associated proteins (β-catenin, Vimentin) and ROR2 in cells was determined by western blot analysis. The potential binding sites were predicted by starBase software online and confirmed by dual-luciferase reporter analysis. The expression of TUG1 and ROR2 was promoted in AS tissues and ox-LDL-treated HA-VSMCs. While the low expression of miR-141-3p negatively correlated with that of TUG1 or ROR2 in AS tissues. Silencing of TUG1 inhibited the proliferation, migration, invasion, and metastasis in ox-LDL-treated HA-VSMCs. Moreover, the putative binding sites between miR-141-3p and TUG1 or ROR2 were predicted by starBase software online. Also, miR-141-3p deletion reversed the positive effects of TUG1 knockdown on cells. Besides, downregulation of miR-141-3p disrupted the biofunctional results from ROR2 silencing. TUG1 enhanced the progression of AS in vitro by regulating the miR-141-3p/ROR2 axis.

Tang Y ，Hu J ，Zhong Z ，Liu Y ，Wang Y ... -  《-》

Myocardial Infarction-associated Transcript Knockdown Inhibits Cell Proliferation, Migration, and Invasion Through miR-490-3p/Intercellular Adhesion Molecule 1 Axis in Oxidized Low-density Lipoprotein-induced Vascular Smooth Muscle Cells.

Ma H ，Zheng L ，Qin H ，Wang W ... -  《-》

HOTTIP knockdown inhibits cell proliferation and migration via regulating miR-490-3p/HMGB1 axis and PI3K-AKT signaling pathway in ox-LDL-induced VSMCs.

Atherosclerosis (AS) is a common cardiovascular disease with complicated pathogenesis. Long non-coding RNAs (lncRNAs) have been reported to be associated with AS progression. We aimed to explore the role and underlying mechanism of HOXA transcript at the distal tip (HOTTIP) in AS. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HOTTIP, miR-490-3p and high mobility group B 1 (HMGB1) in AS patients' sera and oxidized low-density lipoprotein (ox-LDL) induced human aortic vascular smooth muscle cells (HA-VSMCs). Cell Counting Kit-8 (CCK-8) assay and transwell assay were conducted to evaluate the proliferation and migration of HA-VSMCs, respectively. Western blot assay was carried out to determine the levels of proliferating cell nuclear antigen (PCNA), matrix metalloprotein 2 (MMP2), MMP9 and HMGB1. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the targeting association between HOTTIP and miR-490-3p, as well as miR-490-3p and HMGB1. HOTTIP and HMGB1 were upregulated and miR-490-3p was downregulated in the sera of AS patients and ox-LDL-stimulated HA-VSMCs. HOTTIP knockdown suppressed ox-LDL induced proliferation and migration in HA-VSMCs. MiR-490-3p was identified as a target of HOTTIP and HOTTIP overexpression abolished the inhibition on cell proliferation and migration mediated by miR-490-3p in ox-LDL-induced HA-VSMCs. Moreover, miR-490-3p inhibition promoted cell proliferation and migration by directly targeting HMGB1 in ox-LDL-induced HA-VSMCs. Besides, HOTTIP knockdown repressed the activation of PI3K-AKT signaling pathway. HOTTIP knockdown suppressed cell proliferation and migration by regulating miR-490-3p/HMGB1 axis and PI3K-AKT pathway in ox-LDL-induced HA-VSMCs.

Guo X ，Liu Y ，Zheng X ，Han Y ，Cheng J ... -  《-》

Long non-coding RNA MIAT regulates ox-LDL-induced cell proliferation, migration and invasion by miR-641/STIM1 axis in human vascular smooth muscle cells.

Ma G ，Bi S ，Zhang P 《BMC Cardiovascular Disorders》

Circ_0010283/miR-377-3p/Cyclin D1 Axis Is Associated With Proliferation, Apoptosis, Migration, and Inflammation of Oxidized Low-density Lipoprotein-Stimulated Vascular Smooth Muscle Cells.

Circular RNAs have been reported as vital regulators and promising therapeutic targets in multiple human diseases, including atherosclerosis (AS). However, the functional roles of circ_0010283 in AS remain unclear. The real-time quantitative polymerase chain reaction was used to determine the expression levels of circ_0010283, microRNA (miR)-377-3p, and cyclin D1 (CCND1) in serum samples. The vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish the in vitro cell model of AS. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide and clonal colony-forming assays were performed to assess cell proliferation. The apoptosis was determined by flow cytometry assay. The migration of VSMCs was examined by wound healing and transwell assays. Western blot analysis was used to quantify protein expression. The association among circ_0010283, miR-377-3p, and CCND1 was confirmed by dual-luciferase reporter assay. We found that the serum level of circ_0010283 was upregulated in patients with AS and treatment with ox-LDL also increased the expression of circ_0010283 in VSMCs. Treatment with ox-LDL also increased proliferation, migration, and inflammation while inhibited apoptosis in VSMCs, which was overturned by silencing of circ_0010283. Moreover, miR-377-3p was a target of circ_0010283, and downregulation of miR-377-3p counteracted circ_0010283 silencing-induced effects on ox-LDL-stimulated VSMCs. The overexpression of miR-377-3p inhibited proliferation, migration, and inflammation while induced apoptosis of VSMCs by targeting CCND1. CCND1 was a target of miR-377-3p, and circ_0010283 acted as the miR-377-3p sponge to increase CCND1 expression. Circ_0010283 regulated proliferation, apoptosis, migration, and inflammation of ox-LDL-stimulated VSMCs through modulating miR-377-3p and CCND1.

Zhang P ，Wang W ，Li M 《-》