RGD Reference Report - Cardiac-Specific Overexpression of miR-222 Induces Heart Failure and Inhibits Autophagy in Mice. - Rat Genome Database

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Cardiac-Specific Overexpression of miR-222 Induces Heart Failure and Inhibits Autophagy in Mice.

Authors: Su, Ming  Chen, Zhiguo  Wang, Changxin  Song, Lei  Zou, Yubao  Zhang, Lianfeng  Hui, Rutai  Wang, Jizheng 
Citation: Su M, etal., Cell Physiol Biochem. 2016;39(4):1503-11. doi: 10.1159/000447853. Epub 2016 Sep 12.
RGD ID: 151893489
Pubmed: PMID:27614440   (View Abstract at PubMed)
DOI: DOI:10.1159/000447853   (Journal Full-text)


BACKGROUND: MicroRNAs play a crucial role in the regulation of pathological cardiac remodeling and heart failure. Previously, we found that overexpression of miR-221 induces heart failure in mice. The miR-222 and miR-221 share the same gene cluster, however, the role of miR-222 in the regulation of cardiac function remained ill-defined.
METHODS AND RESULTS: Transgenic mice with cardiac-specific expression of miR-222 (Tg-miR-222) mice were generated. The Tg-miR-222 mice developed significantly enlarged hearts at 4 weeks of age. Transthoracic echocardiograph data indicated that the hearts of Tg-miR-222 mice exhibited an increased left ventricular end-diastolic internal diameter and decreased fractional shortening. We observed that the LC3-II in Tg-miR-222 mice was decreased accompanied with the upregulation of p62, indicating the autophagy inhibition in the hearts of Tg-miR-222 mice. The mTOR pathway, a negative regulator of autophagy, was activated in the hearts of Tg-miR-222 mice. The expression of p27 was downregulated by miR-222 overexpression.
CONCLUSION: Our data indicate that miR-222 overexpression induces heart failure in mice. The downregulation of p27 and the activation of mTOR pathway may be involved in miR-222-induced heart failure and autophagy inhibition. Thus, targeting miR-222 expression may be a therapeutic strategy against pathological cardiac remodeling.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiac Fibrosis  ISOMir222 (Mus musculus)151893489; 151893489 RGD 
Cardiac Fibrosis  IDA 151893489 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir222  (microRNA 222)

Genes (Mus musculus)
Mir222  (microRNA 222)

Genes (Homo sapiens)
MIR222  (microRNA 222)


Additional Information