Loss of Lin28a Attenuates Cardiac Hypertrophy Induced by Pressure Overload

Pathological cardiac hypertrophy is a major risk factor for the development of heart failure and sudden cardiac death, yet the molecular mechanism of cardiac hypertrophy is not fully understood. Recently, we found that the expression of Lin28a, a RNA-binding protein, was significantly upregulated during the early stages of cardiac hypertrophy. Interestingly, cardiac specific conditional deletion of Lin28a blunted pressure overload-induced cardiac hypertrophic responses. Given that Lin28a can bind to diverse mRNA to regulate their abundance and/or translation, we conducted RNA-seq to profile the cardiac transcriptome alteration without Lin28a under pressure overload. It showed that metabolic pathways, including glycolysis and biosynthetic pathway, were remarkedly affected. Thus, our study identifies Lin28a as a crucial regulator of cardiac hypertrophy via its role in metabolic programming. Overall design: Cardiac mRNA profiles of cardiac specific Lin28 knockout mice and their control littermates subjected to pressure overload at Day 5 were generated by deep sequencing, in duplicate, using Illumina HiSeq 2500 (50bp x2).