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

• Published in: Life sciences (1973) 2020-05, Vol.248, p.117445-9, Article 117445
• Main Authors: Guo, Xiaoyan, Liu, Yuhao, Zheng, Xiaohui, Han, Yan, Cheng, Jiangtao
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antigens; Aorta; Aorta - metabolism; Aorta - pathology; Arteriosclerosis; Assaying; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - genetics; Atherosclerosis - pathology; Cardiovascular diseases; Case-Control Studies; Cell growth; Cell Line; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cholecystokinin; Female; Gelatinase A; Gelatinase B; Gene Expression Regulation; HA-VSMCs; HMGB1; HMGB1 protein; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; HOTTIP; Humans; Immunoprecipitation; Kinases; Lipoproteins, LDL - pharmacology; Low density lipoprotein; Male; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-490-3p; Muscles; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Non-coding RNA; ox-LDL; Pathogenesis; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Polymerase chain reaction; Proliferating cell nuclear antigen; Proliferating Cell Nuclear Antigen - genetics; Proliferating Cell Nuclear Antigen - metabolism; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Ribonucleic acid; RNA; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; Signaling; Smooth muscle; Target recognition; Transcription
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.117445

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.