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HOTTIP knockdown inhibits cell proliferation and migration via regulating miR-490-3p/HMGB1 axis and PI3K-AKT signaling pathway in ox-LDL-induced VSMCs.
Life Sci. 2020 May 01; 248:117445.LS

Abstract

AIMS

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.

MATERIALS AND METHODS

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.

KEY FINDINGS

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.

SIGNIFICANCE

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

Authors+Show Affiliations

Department of Cardiology, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, China.Department of Cardiology, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, China.Department of Cardiology, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, China.Department of Cardiology, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, China.Department of Cardiology, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: chengjt9888@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32081664

Citation

Guo, Xiaoyan, et al. "HOTTIP Knockdown Inhibits Cell Proliferation and Migration Via Regulating miR-490-3p/HMGB1 Axis and PI3K-AKT Signaling Pathway in ox-LDL-induced VSMCs." Life Sciences, vol. 248, 2020, p. 117445.
Guo X, Liu Y, Zheng X, et al. HOTTIP knockdown inhibits cell proliferation and migration via regulating miR-490-3p/HMGB1 axis and PI3K-AKT signaling pathway in ox-LDL-induced VSMCs. Life Sci. 2020;248:117445.
Guo, X., Liu, Y., Zheng, X., Han, Y., & Cheng, J. (2020). HOTTIP knockdown inhibits cell proliferation and migration via regulating miR-490-3p/HMGB1 axis and PI3K-AKT signaling pathway in ox-LDL-induced VSMCs. Life Sciences, 248, 117445. https://doi.org/10.1016/j.lfs.2020.117445
Guo X, et al. HOTTIP Knockdown Inhibits Cell Proliferation and Migration Via Regulating miR-490-3p/HMGB1 Axis and PI3K-AKT Signaling Pathway in ox-LDL-induced VSMCs. Life Sci. 2020 May 1;248:117445. PubMed PMID: 32081664.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HOTTIP knockdown inhibits cell proliferation and migration via regulating miR-490-3p/HMGB1 axis and PI3K-AKT signaling pathway in ox-LDL-induced VSMCs. AU - Guo,Xiaoyan, AU - Liu,Yuhao, AU - Zheng,Xiaohui, AU - Han,Yan, AU - Cheng,Jiangtao, Y1 - 2020/02/19/ PY - 2019/09/02/received PY - 2020/02/13/revised PY - 2020/02/17/accepted PY - 2020/2/23/pubmed PY - 2020/3/27/medline PY - 2020/2/22/entrez KW - Atherosclerosis KW - HA-VSMCs KW - HMGB1 KW - HOTTIP KW - miR-490-3p KW - ox-LDL SP - 117445 EP - 117445 JF - Life sciences JO - Life Sci. VL - 248 N2 - AIMS: 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. MATERIALS AND METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: HOTTIP knockdown suppressed cell proliferation and migration by regulating miR-490-3p/HMGB1 axis and PI3K-AKT pathway in ox-LDL-induced HA-VSMCs. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/32081664/HOTTIP_knockdown_inhibits_cell_proliferation_and_migration_via_regulating_miR_490_3p/HMGB1_axis_and_PI3K_AKT_signaling_pathway_in_ox_LDL_induced_VSMCs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(20)30193-4 DB - PRIME DP - Unbound Medicine ER -