FTZ protects against cardiac hypertrophy and oxidative injury via microRNA-214 / SIRT3 signaling pathway.

BACKGROUND: Despite the fact that the initial hypertrophic response to ventricular pressure overload is thought to be compensatory, prolonged stress often leads to heart failure. Previous studies have shown that the Fufang-Zhenzhu-Tiaozhi (FTZ) formula is beneficial for the treatment of dyslipidemia and hyperglycemia. However, the effects of FTZ on cardiac hypertrophy remain unclear. OBJECTIVE: The aim of this study is to evaluate the protective effects of FTZ on cardiac hypertrophy and determine the underlying mechanisms. METHODS: TAC was utilized to establish a cardiac hypertrophy animal model, and FTZ was given via gavage for four weeks. Next, echocardiographic measurements were made. The morphology of mouse cardiomyocytes was examined using H&E and WGA staining. In vitro, the neonatal cardiomyocytes were stimulated with angiotensin Ⅱ (Ang Ⅱ). In addition to measuring the size of cardiomyocytes, qRT-PCR and western blotting were conducted to measure cardiac stress markers and pathway. RESULTS: According to our findings, FTZ alleviated cardiac hypertrophy in mice and cell models. Furthermore, expression of miR-214 was down-regulated following FTZ, whereas the effect of FTZ therapy was reversed using miR-214 transfection. Furthermore, the expression of Sirtuin 3 (SIRT3) was decreased in Ang Ⅱ-induced oxidative damage, which was associated with a reduction in SOD-1, GPX1, and HO-1 and an increase in MDA, while SIRT3 expression was restored following FTZ treatment. CONCLUSIONS: Collectively, these findings indicate that FTZ is a protective factor for cardiac hypertrophy due to its regulation of the miR-214-SIRT3 axis, which suggests that FTZ may be a therapeutic target for cardiac hypertrophy.

Transcription factor YY1 inhibits the expression of THY1 to promote interstitial pulmonary fibrosis by activating the HSF1/miR-214 axis.

Interstitial pulmonary fibrosis (IPF) is a progressive disease of diverse etiology manifesting with proliferation of lung fibroblasts and accumulation of extracellular matrix deposition in pulmonary interstitium. Recent studies show aberrant expression of mRNAs and microRNAs (miRNAs) in human embryonic pulmonary fibroblasts (HEPFs). In this study, we investigated effects of the YY1/HSF1/miR-214/THY1 axis on the functions of HEPFs and IPF. Loss- and gain-of-function tests were conducted to identify roles of YY1, HSF1, miR-214, and THY1 in IPF. As determined by RT-qPCR or western blot assay, silencing YY1 down-regulated HSF1 expression and attenuated the expression of pro-proliferative and fibrosis markers in HEPFs. Meanwhile, viability of HEPFs was impeded by YY1 knockdown. The binding relationship between miR-214 and THY1 was verified using dual-luciferase reporter assay. In HEPFs, down-regulation of HSF1 reduced miR-214 expression to repress proliferation and fibrogenic transformation of HEPFs, while inhibition of miR-214 expression could restrain the fibrogenic transformation property of HEPFs by up-regulating THY1. Subsequently, IPF model in mice was induced by bleomycin treatment. These animal experiments validated the protective effects of YY1 knockdown against IPF-induced lung pathological manifestations, which could be reversed by THY1 knockdown. Our study demonstrates the important involvement of YY1/HSF1/miR-214/THY1 axis in the development of IPF.

Formononetin inhibits osteosarcoma cell proliferation and promotes apoptosis by regulating the miR-214-3p/phosphatase and tensin homolog pathway.

BACKGROUND: Phytoestrogens have a similar molecular structure to estrogens which can produce either estrogenic or anti-estrogenic effects. It is generally believed that phytoestrogens combine with the estrogen receptor of osteosarcoma cells, affecting a variety of signal transduction pathways and cell metabolism, resulting in altered cell proliferation, differentiation, apoptosis, invasion and migration ability. Formononetin (FN) is the active ingredient of traditional Chinese medicine astragalus, angelica, and Pueraria lobate. Our study aims to detect the role of FN on MG-63 cell viability and apoptosis through regulating phosphatase and tensin homolog (PTEN) expression via MicroRNA-214-3p (miR-214-3p). METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Caspase 3 assay evaluated cell viability and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot evaluated the mRNA and protein expressions, respectively. The binding site of miR-214-3p/PTEN was detected via dual luciferase assay. RESULTS: FN suppressed cell viability and induced apoptosis, and decreased miR-214-3p level and promoted PTEN expression. PTEN was then regarded as a target of miR-214-3p, and FN improved PTEN level via inhibiting miR-214-3p. Further analysis showed that overexpressed miR-214-3p improved cell viability and suppressed apoptosis of MG-63 cells by inhibiting PTEN expression. CONCLUSIONS: Finally, our results revealed that FN inhibited cell viability and induced apoptosis by regulating miR-214-3p. FN acted as a new treatment for MG-63 cells via increasing PTEN level by inhibiting the miR-214-3p level.