Background: Aberrant expression of circular RNAs contributes to the initiation and progression of cancers, but the underlying mechanism remains elusive. Methods: RNA-seq and qRT-PCR were performed to screen differential expressed circRNAs between gastric cancer tissues and adjacent normal tissues. Candidate circRNA (circMRPS35) was screened out and validated by qRT-PCR. Cell proliferation and invasion ability were determined by CCK-8 and cell invasion assays. RNA-seq, GO-pathway, RNA pull-down and ChIRP were further applied to search for detailed mechanism. Results: Here, a novel circRNA named circMRPS35, was screened out by RNA-seq in gastric cancer tissues, whose expression is related to clinicopathological characteristics and prognosis in gastric cancer patients. Biologically, circMRPS35 suppresses the proliferation and invasion of gastric cancer cells in vitro and in vivo. Mechanistically, circMRPS35 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of FOXO1 and FOXO3a genes, which elicits acetylation of H4K5 in their promoters. Particularly, circMRPS35 specifically binds to FOXO1/3a promoter regions directly. Thus, it dramatically activates the transcription of FOXO1/3a and triggers subsequent response of their downstream target genes expression, including p21, p27, Twist1 and E-cadherin, resulting in the inhibition of cell proliferation and invasion. Moreover, circMRPS35 expression positively correlates with that of FOXO1/3a in gastric cancer tissues. Conclusions: Our findings not only reveal the pivotal roles of circMRPS35 in governing histone modification in anticancer treatment, but also advocate for triggering circMRPS35/KAT7/FOXO1/3a pathway to combat gastric cancer.
The root of Panax notoginseng, a highly valued medicine and functional food, is the main part used for medicinal purposes. However, the stems and leaves are also used in practice. To provide a chemical basis for various uses, a quantitative comparison of 18 saponins using a non-targeted metabolomics approach was established, so as to investigate the chemical profiles of the different parts of P. notoginseng. The established strategy revealed that roots and stems, with their similar chemical characteristics, consisted mainly of protopanaxatriol-type saponins, whereas protopanaxadiol-type saponins were principally present in the leaves. Multivariate analysis further suggested that the quality of the stems and leaves of P. notoginseng was significantly affected by its geographical origin. Furthermore, 52 constituents (26 non-volatile and 26 volatile) were identified as potential markers for discriminating between different parts of the plant. Taken together, the study provides comprehensive chemical evidence for the rational application and exploitation of different parts of P. notoginseng.
Quality assessment of Cortex Periplocae remains a challenge, due to its complex chemical profile. This study aims to investigate the chemical components of Cortex Periplocae, including its non-volatile and volatile constituents, via liquid chromatograph–mass spectrometry (LC-MS/MS) and gas chromatography–mass spectrometry (GC-MS) assays. The established strategy manifested that Cortex Periplocae from different producing areas was determined by identifying 27 chemical markers with ultra-high-performance liquid chromatography, coupled with quadrupole tandem time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), including four main groups of cardiac glycosides, organic acids, aldehydes, and oligosaccharides. These groups’ variable importance in the projection (VIP) were greater than 1. Simultaneously, the samples were divided into four categories, combined with multivariate statistical analysis. In addition, in order to further understand the difference in the content of samples from different producing areas, nine chemical markers of Cortex Periplocae from 14 different producing areas were determined by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS), and results indicated that the main effective constituents of Cortex Periplocae varied with places of origin. Furthermore, in GC-MS analysis, samples were divided into three groups with multivariate statistical analysis; in addition, 22 differential components whose VIP were greater than 1 were identified, which were principally volatile oils and fatty acids. Finally, the relative contents of seven main volatile constituents were obtained, which varied extremely with the producing areas. The results showed that the LC-MS/MS and GC-MS assays, combined with multivariate statistical analysis for Cortex Periplocae, provided a comprehensive and effective means for its quality evaluation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.