# Role of miR-574-Fam210a axis in cardiac hypertrophy and remodeling

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $385,000

## Abstract

Project Summary:
Heart Failure (HF) results from cardiomyocyte (CM) hypertrophy and apoptosis, combined with
cardiac fibroblast (CF) proliferation and fibrosis; these are hallmarks of cardiac pathological
remodelling, which is accompanied by changes in the expression of specific miRNAs and
mitochondrial-encoded genes (MEGs). Early stage cardiac hypertrophy (CH) induces compensatory
mitochondrial protein translation. Endpoint HF is accompanied by reduced mitochondrial protein
synthesis and dysfunctional mitochondria. It is generally accepted that restoring mitochondrial protein
expression and function mitigates HF progression, highlighting the importance of clarifying gene
regulation mechanisms in mitochondria to guide development of improved HF therapeutics. Many
studies have examined mechanisms that coordinate mRNA transcription of nuclear-encoded
mitochondrial genes (NEMGs) and MEGs. However, regulatory mechanisms of MEG mRNA
translation and its coordination with NEMG mRNA translation in the heart remain virtually unexplored.
We have identified a miR-574-Fam210a axis that maintains the optimal translation of MEGs and
mitochondrial homeostasis in both CM and CF, as a compensatory cardioprotective pathway at an
early stage of CH. In contrast to most other single strand miRNAs, miR-574 produces 2 functional
strands, miR-574-5p and miR-574-3p. At early stage of CH, miR-574-5p antagonizes Fam210a
expression in CM to prevent excessive MEG expression, enhanced ROS production and impaired
mitochondrial activity, thereby preventing CM hypertrophy and apoptosis. Moreover, hypertrophic
stress activates Src kinase-mediated Tyr359 phosphorylation and cytoplasmic accumulation of hnRNP
L in CM. P-hnRNP L captures miR-574-3p and promotes exosome-mediated release of miR-574-3p
and reduces cardiac fibroblasts (CF) proliferation by targeting CF Fam210a. Our central hypothesis is:
in CM and CF, miR-574-Fam210a axis maintains optimal translation of mitochondrial-encoded genes
and mitochondrial homeostasis, thereby limiting pathological cardiac hypertrophy and ventricular
remodeling. We will test this hypothesis by pursuing 3 aims. Aim 1. Elucidate the mechanism of guide
strand miR-574-5p in preventing pathological cardiac hypertrophy and CM apoptosis. Aim 2. Establish
the role and mechanism of passenger strand miR-574-3p in antagonizing cardiac fibrosis. Aim 3.
Determine the function and mechanism of Fam210a in mitochondrial translational control and
regulation of cardiac function.

## Key facts

- **NIH application ID:** 9988261
- **Project number:** 5R01HL132899-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Peng Yao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988261

## Citation

> US National Institutes of Health, RePORTER application 9988261, Role of miR-574-Fam210a axis in cardiac hypertrophy and remodeling (5R01HL132899-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9988261. Licensed CC0.

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