Qishen Yiqi dropping pills improve cardiomyocyte hypertrophy via the lncRNA TINCR/miR-193b-3p/RORA axis

Abstract

Background This study was designed to explore the therapeutic effect and mechanism of action of Qishen Yiqi dropping pills (QYDP) in chronic heart failure (CHF) via a long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) axis. Here, the mechanism of action of the lncRNA terminal differentiation-induced non-coding RNA (TINCR), miR-193b-3p, and RAR-related orphan receptor A (RORA) mRNA was analyzed in an angiotensin (Ang) II-induced H9C2 cardiomyocyte hypertrophy model treated with QYDP. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the gene expression changes of lncRNA, miRNA, and mRNA in H9C2 induced by QYDP on Ang II. The Gene Expression Omnibus (GEO) was used to analyze differentially expressed genes (DEGs) potentially affecting CHF progression. Cell Counting Kit-8 (CCK-8) was used to analyze the effect of QYDP on the proliferation of H9C2, RNA pull-down was used to analyze the binding of lncRNA and miRNA, and dual luciferase was used to analyze the targeting of miRNA and lncRNA or mRNA. Results Ang II induced TINCR and RORA downregulation, miR-193b-3p upregulation, and hypertrophy in the H9C2 cardiomyocytes, which were alleviated by QYDP. In contrast, TINCR inhibition reversed the effects of QYDP by increasing miR-193b-3p expression and downregulating RORA expression. According to subsequent double luciferase and RNA pull-down experiments, TINCR adsorbed miR-193b-3p by acting as a competitive endogenous RNA sponge and miR-193b-3p directly targeted RORA. Lastly, we showed that the Ang-II-induced inhibition of TINCR and RORA expression and promotion of cardiac hypertrophy were both reversed by a TINCR overexpression plasmid (ov-TINCR), whereas the effects of ov-TINCR were suppressed by a miR-193b-3p mimic. Conclusions Administration of QYDP improves Ang II-induced H9C2 cardiomyocyte hypertrophy and increase cell proliferation rate through the TINCR/miR-193b-3p/RORA axis.

Synaptotagmin-1 attenuated myocardial programmed necrosis and ischemia/reperfusion injury through the mitochondrial pathway

“…MiR-193b-3p regulates cardiac necrosis and I/R injury Recent advances have revealed that miR-193b-3p participates in the regulation of pulmonary hypertension in heart failure[36], cardiac hypertrophy [37] and apoptotic pathway in myocardial I/R injury [38]. However, the role of miR-193b-3p in cardiac programmed necrosis has not been clari ed.…”

“…Previous studies on the functions of miR-193b-3p were mainly focused on tumor [47,48], in ammation [49,50], and metabolism [36,51]. Recent advances have revealed that miR-193b-3p participates in the regulation of pulmonary hypertension in heart failure[36], cardiac hypertrophy [37] and the apoptotic pathway in myocardial ischemia/reperfusion injury [38]. However, the roles of miR-193b-3p in the cardiomyocyte necrotic death have not been explored.…”

Determination of Four Chemical Components in Qishen Yiqi Dripping Pills by UPLC-MS/MS Method

“…Clinically, Zhang et al (2022) proved that it mainly treats symptoms of qi deficiency and blood stasis, such as chest tightness and chest pain, shortness of breath, and spontaneous sweating. Chen L, et al (2022) found that Qishen Yiqi dripping pills mainly play an auxiliary role in the treatment of patients with coronary heart disease, and Chen W, et al (2022) demonstrated that Qishen Yiqi dripping pills could be combined with Western medicine to treat diseases such as hypertension and angina.…”