LukS-PV Inhibits Hepatocellular Carcinoma Cells Migration via the TNNC1/PI3K/AKT Axis
ONCOTARGETS AND THERAPY
Authors: Ma, Fan; Wang, Ziran; Qiang, Yawen; Xu, Liangfei; Ding, Pengsheng; Wang, Yangyan; Ma, Xiaoling
Abstract
Purpose: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. LukS-PV is the S component of Panton-Valentine leucocidin (PVL), a toxin secreted by Staphylococcus aureus. We aimed to investigate the role of LukS-PV in HCC cell migration and the specific molecular mechanism involved. Methods: We used scratch assays to detect the mobility of liver cancer cells treated with LukS-PV. Quantitative real-time PCR and Western blot analysis were performed to detect the expression levels of related genes. RNA sequencing and quantitative proteomics sequencing were used to assess the transcriptional and proteomic alterations of target genes. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway analyses revealed the downstream signaling pathway targets of LukS-PV. Results: Our results demonstrated that LukS-PV could inhibit HCC cell migration in a concentration-dependent manner. LukS-PV could also downregulate the expression of TNNC1, which was highly expressed in HCC cells. Additionally, the study showed that LukS-PV inhibited HCC cell migration by downregulating TNNC1. Further studies showed that LukS-PV inhibited the phosphorylation of PI3K/AKT pathway by targeting TNNC1, thereby inhibiting HCC cell migration. Conclusion: Our study demonstrated that LukS-PV has an inhibitory role in the migration of liver cancer cells through the TNNC1/PI3K/AKT axis.
iTRAQ-Based Proteomic Analysis Reveals Recovery of Impaired Mitochondrial Function in Ischemic Myocardium by Shenmai Formula
JOURNAL OF PROTEOME RESEARCH
Authors: Wang, Yi; Zhao, Yu; Jiang, Wei; Zhao, Xiaoping; Fan, Guanwei; Zhang, Han; Shen, Peiqiang; He, Jiangmin; Fan, Xiaohui
Abstract
Shenmai formula (SM) has been a traditional medicinal remedy for treating cardiovascular diseases in China for 800 years; however, its mechanism of action remains unclear. To explore the mechanism underlying cardioprotective effects of SM, iTRAQ:based proteomic approach was applied to analyze protein of myocardium in rats with myocardial ischemic injury. Upon treatment with SM and its two major components Red ginseng (RG) and Radix Ophiopogonis (OP), 101 differentially expressed proteins were filtered from a total of 712 detected and annotated proteins. They can be classified according to their locations and functions, while most of them are located in intracellular organelle, participating in cellular metabolic process. The functions of them are mostly associated with mitochondrial oxidative phosphorylation/respiration. The differentially expressed proteins were validated by liquid chromatography tandem mass spectrometry and Western blotting (ATP5D, NDUFB10, TNNC1). Further in vitro experiments found that SM could attenuate hypoxia induced impairment of mitochondrial membrane potential and cellular ATP concentration in neonatal rat ventricular myocytes. Interestingly, the result of quantitative mitochondrial biogenesis assays revealed that SM had dominant positive effects on the maximum respiration, ATP-coupled respiration, and spare capacity of mitochondria in response to hypoxia. Hence, our findings suggest that SM promotes mitochondrial function to protect cardiomyocytes against hypoxia, which provides a possible illustration for conventional botanical therapy on a molecular level.