Long non‑coding RNA MALAT1 sponges miR‑124‑3p.1/KLF5 to promote pulmonary vascular remodeling and cell cycle progression of pulmonary artery hypertension
| العنوان: | Long non‑coding RNA MALAT1 sponges miR‑124‑3p.1/KLF5 to promote pulmonary vascular remodeling and cell cycle progression of pulmonary artery hypertension |
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| المؤلفون: | Hong Pan, Shuyun Jiang, Dapeng Wang, Bo Wu, Ruilan Wang, Jingyu Chen, Hongyang Xu |
| المصدر: | International Journal of Molecular Medicine |
| بيانات النشر: | Spandidos Publications, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Vascular smooth muscle, Adolescent, proliferation, Myocytes, Smooth Muscle, Cell, Kruppel-Like Transcription Factors, Vascular Remodeling, Muscle, Smooth, Vascular, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Genes, Reporter, Cell Line, Tumor, Genetics, medicine, Humans, Gene silencing, human pulmonary artery smooth muscle cells, Cell Proliferation, Gene knockdown, MALAT1, Chemistry, Cell Cycle, Endothelial Cells, Articles, General Medicine, Middle Aged, Cell cycle, Kruppel-like factor 5, Molecular medicine, hsa-microRNA-124-3p.1, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Female, RNA, Long Noncoding, metastasis-associated lung adenocarcinoma transcript 1, G1 phase, pulmonary artery hypertension, Signal Transduction |
| الوصف: | Previous studies have demonstrated that long non‑coding RNA (lncRNA) is involved in vascular remodeling. The metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) lncRNA is associated with the proliferation and migration of vascular smooth muscle and endothelial cells; however, its biological role in pulmonary artery hypertension (PAH) is currently unclear. The aim of the present study was to investigate the post‑transcriptional regulation of MALAT1 in human pulmonary artery smooth muscle cells (HPASMCs). The results revealed that MALAT1 expression levels were significantly upregulated in the pulmonary arteries (PAs) and HPASMCs obtained from patients with PAH compared with adjacent normal PA tissues and HPASMCs. Knockdown of MALAT1 suppressed the viability and proliferation of HPASMCs and prevented cells entering the G0/G1 cell cycle phase. MALAT1 overexpression exerted the opposite effects. Bioinformatics analysis predicted complementary binding of hsa‑microRNA (miR)‑124‑3p.1 with the 3'‑untranslated region of MALAT1. Luciferase reporter assays and RNA immunoprecipitation experiments demonstrated molecular binding between MALAT1 and hsa‑miR‑124‑3p.1. This resulted in the formation of an RNA‑induced silencing complex. In addition, Kruppel‑like factor 5 (KLF5) was confirmed to be a target gene of MALAT1/hsa‑miR‑124‑3p.1. MALAT1 silencing did not inhibit the proliferation and migration of HPASMCs following knockdown of hsa‑miR‑124‑3p.1. In addition, MALAT1 knockdown was demonstrated to attenuate the expression of KLF5. Following MALAT1 knockdown, the expression level of KLF5 was rescued by inhibition of hsa‑miR‑124‑3p.1 expression. The results of the current study indicate that the MALAT1/hsa‑miR‑124‑3p.1/KLF5 axis may serve a key role in HPASMCs. In addition, the results contribute to what is known regarding the role of MALAT1 in PAH development and provide a novel theoretical basis for the development of new therapeutic interventions for patients with PAH. |
| تدمد: | 1791-244X 1107-3756 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7dd1f61adc35fdea4f1f05c6e7072d9aTest https://doi.org/10.3892/ijmm.2019.4256Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7dd1f61adc35fdea4f1f05c6e7072d9a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1791244X 11073756 |
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