Dataset Information

Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats.

ABSTRACT: Exercise-induced autophagy is associated with physiological left ventricular hypertrophy (LVH), and a growing body of evidence suggests that microRNAs (miRNAs) can regulate autophagy-related genes. However, the precise role of miRNAs in exercise induced autophagy in physiological LVH has not been fully defined. In this study, we investigated the microRNA-autophagy axis in physiological LVH and deciphered the underlying mechanism using a rat swimming exercise model. Rats were assigned to sedentary control (CON) and swimming exercise (EX) groups; those in the latter group completed a 10-week swimming exercise without any load. For in vitro studies, H9C2 cardiomyocyte cell line was stimulated with IGF-1 for hypertrophy. We found a significant increase in autophagy activity in the hearts of rats with exercise-induced physiological hypertrophy, and miRNAs showed a high score in the pathway enriched in autophagy. Moreover, the expression levels of miR-26b-5p, miR-204-5p, and miR-497-3p showed an obvious increase in rat hearts. Adenovirus-mediated overexpression of miR-26b-5p, miR-204-5p, and miR-497-3p markedly attenuated IGF-1-induced hypertrophy in H9C2 cells by suppressing autophagy. Furthermore, miR-26b-5p, miR-204-5p, and miR-497-3p attenuated autophagy in H9C2 cells through targeting ULK1, LC3B, and Beclin 1, respectively. Taken together, our results demonstrate that swimming exercise induced physiological LVH, at least in part, by modulating the microRNA-autophagy axis, and that miR-26b-5p, miR-204-5p, and miR-497-3p may help distinguish physiological and pathological LVH.

SUBMITTER: Qi J

PROVIDER: S-EPMC7042403 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats.

Qi Jie J Luo Xue X Ma Zhichao Z Zhang Bo B Li Shuyan S Zhang Jun J

Frontiers in genetics 20200219

Exercise-induced autophagy is associated with physiological left ventricular hypertrophy (LVH), and a growing body of evidence suggests that microRNAs (miRNAs) can regulate autophagy-related genes. However, the precise role of miRNAs in exercise induced autophagy in physiological LVH has not been fully defined. In this study, we investigated the microRNA-autophagy axis in physiological LVH and deciphered the underlying mechanism using a rat swimming exercise model. Rats were assigned to sedentar ...[more]

PMID: 32140172

Similar Datasets

Project description:Onconase (ONC) is an amphibian secretory ribonuclease displaying cytostatic and cytotoxic activities against many mammalian tumors, including melanoma. ONC principally damages tRNA species, but also other non-coding RNAs, although its precise targets are not known. We investigated the ONC ability to modulate the expression of 16 onco-suppressor microRNAs (miRNAs) in the A375 BRAF-mutated melanoma cell line. RT-PCR and immunoblots were used to measure the expression levels of miRNAs and their regulated proteins, respectively. In silico study was carried out to verify the relations between miRNAs and their mRNA targets. A375 cell transfection with miR-20a-3p and miR-34a-5p mimics or inhibitors was performed. The onco-suppressors miR-20a-3p, miR-29a-3p and miR-34a-5p were highly expressed in 48-h ONC-treated A375 cells. The cytostatic effect of ONC in A375 cells was mechanistically explained by the sharp inhibition of cyclins D1 and A2 expression level, as well as by downregulation of retinoblastoma protein and cyclin-dependent-kinase-2 activities. Remarkably, the expression of kinases ERK1/2 and Akt, as well as of the hypoxia inducible factor-1α, was inhibited by ONC. All these proteins control pro-survival pathways. Finally, many crucial proteins involved in migration, invasion and metastatic potential were downregulated by ONC. Results obtained from transfection of miR-20a-3p and miR-34a-5p inhibitors in the presence of ONC show that these miRNAs may participate in the antitumor effects of ONC in the A375 cell line. In conclusion, we identified many intracellular downregulated proteins involved in melanoma cell proliferation, metabolism and progression. All mRNAs coding these proteins may be targets of miR-20a-3p, miR-29a-3p and/or miR-34a-5p, which are in turn upregulated by ONC. Data suggest that several known ONC anti-proliferative and anti-metastatic activities in A375 melanoma cells might depend on the upregulation of onco-suppressor miRNAs. Notably, miRNAs stability depends on the upstream regulation by long-non-coding-RNAs or circular-RNAs that can, in turn, be damaged by ONC ribonucleolytic activity.

Dataset Information

Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats.

Publications

Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets