Back to Search
Start Over
miR-496 remedies hypoxia reoxygenation-induced H9c2 cardiomyocyte apoptosis via Hook3-targeted PI3k/Akt/mTOR signaling pathway activation.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2020 Jan; Vol. 121 (1), pp. 698-712. Date of Electronic Publication: 2019 Aug 22. - Publication Year :
- 2020
-
Abstract
- The hypoxia-reoxygenation (H/R) model helps analyze myocardial infarction triggered by acute myocardial ischemia, which induces cardiomyocyte proliferation and apoptosis. The Gene Expression Omnibus database was used to obtain the GSE74205 and GSE3866 microarray data, including microRNA (miRNA) and messenger RNA profiles, to catalog potential key miRNAs and genes. The role of rno-mir-496 expression in cardiomyocyte proliferation within 10 days of birth was established. The microRNA Target Prediction Database (miRDB) database-via Gene Ontology annotation-predicted hook microtubule tethering protein 3 (Hook3), a key target gene of rno-mir-496, was closely related to cell proliferation. Upregulation of miR-496 related to a significant reduction in apoptosis of H9c2 and human cardiomyocytes treatment with H/R. Moreover, transfection of H9c2 cells with miR-496 mimics, which were pretreated with H/R for 12 hours, increased Ki67 levels, proliferating cell nuclear antigen and Bcl-2 proteins; and decreased cleaved caspase-3 and Bax protein levels, as determined by reverse transcription-polymerase chain reaction and Western blot assays. A dual-luciferase reporter system confirmed that miR-496 targets the Hook3 suppressor. Hook3 overexpression stimulated apoptosis in H/R-treated cells, thus reducing cell proliferation. Upregulated miR-496 activated phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling, while Hook3 exhibited the inverse trend in H/R-treated H9c2 cells. In summary, with Hook3 functionality's aid, miR-496 upregulation defends cells from H/R-induced apoptosis and stimulates cell proliferation. miR-496 targets Hook3 to trigger the PI3K/Akt/mTOR signaling pathway for antiapoptotic and proliferative effects.<br /> (© 2019 Wiley Periodicals, Inc.)
- Subjects :
- Animals
Apoptosis
Cell Hypoxia
Cell Proliferation
Cells, Cultured
Humans
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Myocardial Reperfusion Injury genetics
Myocardial Reperfusion Injury metabolism
Myocytes, Cardiac metabolism
Phosphatidylinositol 3-Kinases genetics
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
Rats
Signal Transduction
TOR Serine-Threonine Kinases genetics
TOR Serine-Threonine Kinases metabolism
Gene Expression Regulation
MicroRNAs genetics
Myocardial Reperfusion Injury pathology
Myocytes, Cardiac pathology
Oxygen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4644
- Volume :
- 121
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31436348
- Full Text :
- https://doi.org/10.1002/jcb.29316