AbstractLong noncoding RNAs (lncRNAs) are known to participate in the pathological process of cardiac hypertrophy. This study aimed to investigate the function of the lncRNA, myosin heavy-chain associated RNA transcript (Mhrt), in cardiac hypertrophy and its possible mechanism of action. Adult mouse cardiomyocytes were treated with angiotensin II (Ang II) and transfected withMhrt; cardiac hypertrophy was evaluated by estimating atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy-chain levels, and cell surface area by reverse transcription-quantitative polymerase chain reaction, western blotting, and immunofluorescence staining. The interaction between theMhrt/Wnt family member 7B (WNT7B) and miR-765 was assessed using a luciferase reporter assay. Rescue experiments were performed by analyzing the role of the miR-765/WNT7B pathway underlying the function ofMhrt. The results indicated that Ang II induced hypertrophy of cardiomyocytes; however, overexpression ofMhrtalleviated the Ang II-induced cardiac hypertrophy.Mhrtacted as a sponge for miR-765 to regulate the expression of WNT7B. Rescue experiments revealed that the inhibitory effect ofMhrton myocardial hypertrophy was abolished by miR-765. Additionally, the knockdown of WNT7B reversed the suppression of myocardial hypertrophy induced by downregulating miR-765. Taken together,Mhrtalleviated cardiac hypertrophy by targeting the miR-765/WNT7B axis.