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LncRNA CASC2 inhibits hypoxia-induced pulmonary artery smooth muscle cell proliferation and migration by regulating the miR-222/ING5 axis.
- Source :
- Cellular & Molecular Biology Letters; 3/17/2020, Vol. 25 Issue 1, p1-16, 16p
- Publication Year :
- 2020
-
Abstract
- Background: Pulmonary arterial hypertension (PAH) is often characterized by cell proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). LncRNA cancer susceptibility candidate 2 (CASC2) has been revealed to be involved in PASMC injury in hypoxia-induced pulmonary hypertension. However, the exact molecular mechanisms whereby CASC2 regulates PASMC proliferation and migration are still incompletely understood. Methods: The expression levels of CASC2, miR-222 and inhibitor of growth 5 (ING5) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot, respectively. Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. Wound healing assay was used to analyze cell migration ability. The relationship between miR-222 and CASC2 or ING5 was confirmed using bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay. Results: CASC2 was down-regulated in hypoxia-induced PASMCs in a dose- and time-dependent manner. Functional experiments showed that CASC2 overexpression could reverse hypoxia-induced proliferation and migration of PASMCs. Bioinformatics analysis indicated that CASC2 acted as a competing endogenous RNA of miR-222, thereby regulating the expression of ING5, the downstream target of miR-222, in PASMCs. In addition, rescue assay suggested that the inhibition mediated by CASC2 of hypoxia-induced PASMC proliferation and migration could be attenuated by miR-222 inhibition or ING5 overexpression. Conclusion: CASC2 attenuated hypoxia-induced PASMC proliferation and migration by regulating the miR-222/ING5 axis to prevent vascular remodeling and the development of PAH, providing a novel insight and therapeutic strategy for hypoxia-induced PAH. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14258153
- Volume :
- 25
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Cellular & Molecular Biology Letters
- Publication Type :
- Academic Journal
- Accession number :
- 142293587
- Full Text :
- https://doi.org/10.1186/s11658-020-00215-y