PurposeGastric cancer is a common tumor of the digestive system. Identification of potential molecules associated with gastric cancer progression and validation of potential biomarkers for gastric cancer diagnosis are very important. Thus, the aim of our study was to determine the serum metabolic characteristics of the serum of patients with chronic gastritis (CG) or gastric cancer (GC) and validate candidate biomarkers for disease diagnosis.Experimental DesignA total of 123 human serum samples from patients with CG or GC were collected for untargeted metabolomic analysis via UHPLC-Q-TOF/MS to determine characteristics of the serum. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and heat map were used for multivariate analysis. In addition, commercial databases were used to identify the pathways of metabolites. Differential metabolites were identified based on a heat map with a t-test threshold (p < 0.05), fold-change threshold (FC > 1.5 or FC < 2/3) and variable importance in the projection (VIP >1). Then, differential metabolites were analyzed by receiver operating characteristic (ROC) curve to determine candidate biomarkers. All samples were analyzed for fasting lipid profiles.ResultsAnalysis of serum metabolomic profiles indicated that most of the altered metabolic pathways in the three groups were associated with lipid metabolism (p < 0.05) and lipids and lipid-like molecules were the predominating metabolites within the top 100 differential metabolites (p < 0.05, FC > 1.5 or FC < 2/3, and VIP >1). Moreover, differential metabolites, including hexadecasphinganine, linoleamide, and N-Hydroxy arachidonoyl amine had high diagnostic performance according to PLS-DA. In addition, fasting lipid profile analysis showed the serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (Apo-A1) were decreased concomitant to the progression of the progression of the disease compared with those in the control group (p < 0.05).ConclusionsThus, this study demonstrated that lipid metabolism may influence the development of CG to GC. Hexadecasphinganine, linoleamide, and N-Hydroxy arachidonoyl amine were selected as candidate diagnostic markers for CG and GC.

Renal cell carcinoma (RCC) is a common urologic malignancy, and up to 30% of RCC patients present with locally advanced or metastatic disease at the time of initial diagnosis. Increasing evidence suggests that circular RNAs (circRNAs) serve as genomic regulatory molecules in various human cancers. Our initial in silico microarray‐based analysis identified that circRNA circ_001842 was highly expressed in RCC. Such up‐regulation of circ_001842 in RCC was experimentally validated in tissues and cell lines using RT‐qPCR. Thereafter, we attempted to identify the role of circ_001842 in the pathogenesis of RCC. Through a series of gain‐ and loss‐of function assays, cell biological functions were examined using colony formation assay, Transwell assay, annexin V‐FITC/PI‐labelled flow cytometry and scratch test. A high expression of circ_001842 in tissues was observed as associated with poor prognosis of RCC patients. circ_001842 was found to elevate SLC39A14 expression by binding to miR‐502‐5p, consequently resulting in augmented RCC cell proliferation, migration and invasion, as well as EMT in vitro and tumour growth in vivo. These observations imply the involvement of circ_001842 in RCC pathogenesis through a miR‐502‐5p‐dependent SLC39A14 mechanism, suggesting circ_001842 is a potential target for RCC treatment.

ZNF143, a human homolog of the transcriptional activator Staf, is a C2H2-type protein consisting of seven zinc finger domains. As a transcription factor (TF), ZNF143 is sequence specifically binding to chromatin and activates the expression of protein-coding and non-coding genes on a genome scale. Although it is ubiquitous expressed, its expression in cancer cells and tissues is usually higher than that in normal cells and tissues. Therefore, abnormal expression of ZNF143 is related to cancer cell survival, proliferation, differentiation, migration, and invasion, suggesting that new small molecules can be designed by targeting ZNF143 as it may be a good potential biomarker and therapeutic target for related cancers. However, the mechanism on how ZNF143 regulates its targeting gene remains unclear. Recently, with the development of chromatin conformation capture (3C) and its derivatives, and high-throughput sequencing technology, new findings have been obtained in the study of ZNF143. Pioneering studies have showed that ZNF143 binds directly to promoters and contributes to chromatin interactions connecting promoters to distal regulatory elements, such as enhancers. Further, it has proved that ZNF143 is involved in CCCTCbinding factor (CTCF) in establishing the conserved chromatin loops by cooperating with cohesin and other partners. These results indicate that ZNF143 is a key loop formation factor. In addition, we report ZNF143 is dynamically bound to chromatin during the cell cycle demonstrated that it is a potential mitotic bookmarking factor. It may be associated with CTCF for mitosis-to-G1 phase transition and chromatin loop re-establishment in early G1 phase. In the future, researchers could further clarify the fine mechanism of ZNF143 in mediating chromatin loops with the help of CUT&RUN (CUT&Tag) and Cut-C technology. Thus, in this review, we summarize the research progress of TF ZNF143 in detail and also predict the potential functions of ZNF143 in cell fate and identity based on our recent discoveries.

Background. Previous studies have demonstrated that lncRNAs play functional roles in regulating cancer cell proliferation, invasion, and apoptosis. Recent studies confirmed that lncRNA 00312 has important biological functions in lung and colorectal cancer. However, the role of lncRNA 00312 in renal cell carcinoma (RCC) remains unclear. Our aim was to explore the function of lncRNA 00312 in RCC and its potential molecular mechanism. Methods. RCC cell lines A498 and ACHN were used as in vitro models in this study. RT-PCR was performed to determine lncRNA 00312, miR-34a-5p, and ASS1 mRNA expression. Proliferation and invasion were examined by CCK-8 and Transwell assay to confirm the function role of lncRNA 00312. Western blot analysis was used to examine the expression of apoptotic proteins Bax and Bcl-2. Results. lncRNA was significantly downregulated in RCC cells such as A498 and ACHN; the expression of lncRNA 00312 in RCC tissues was significantly lower than that in adjacent normal tissues. Patients with low expression of lncRNA 00312 have worse prognosis regarding pathological grade, tumor size, and TNM stage. Overexpression of lncRNA 00312 suppressed A498 and ACHN cell proliferation and invasion, while promoting apoptosis. Our study found that miR-34a-5p had the potential binding site with lncRNA 00312 and revealed the role of miR-34a-5p in RCC. Furthermore, we confirmed that lncRNA 00312 played its role with the participation of ASS1 and miR-34a-5p. Conclusion. lncRNA 00312 can inhibit RCC proliferation and invasion and promote apoptosis in vitro by suppressing miR-34a-5p and overexpressing ASS1. Our study demonstrated that the lncRNA 00312/miR-34a-5p/ASS1 axis may play a functional role in the progression of RCC; lncRNA 00312 abundance is a prognostic factor candidate for RCC survival, which provides new insights for RCC clinical treatment.

Objective Diabetic kidney disease (DKD) leads to low high albuminuria and gradually progresses to very high albuminuria with kidney insufficiency. However, about 20–40% of DKD is normoalbuminuric DKD (NADKD), which has impaired kidney function but normal urine albumin. This study is to investigate the urine metabolomic profiles of patients with NADKD and albuminuria DKD (ADKD). Methods In total, 95 patients were divided into a simple diabetes mellitus group (SDM group), an ADKD group, and a NADKD group. All subjects were analyzed for urine metabolites using non-targeted metabolomics based on ultra-performance liquid chromatography – tandem mass spectrometry. Results The urine metabolomic profiles of the SDM group, NADKD group, and ADKD group were significantly different, and 65 different metabolites were identified among the three groups. Metabolic pathway analysis of these differential metabolites found that the top three significantly changed metabolic pathways were linoleic acid metabolism, citrate cycle, and, arginine and proline metabolism. There are 12 metabolites enriched in these three metabolic pathways. In detail, compared with those in the SDM group, the levels of γ-linolenic acid in the ADKD group were increased significantly, while the levels of succinic acid, cis -aconitic acid, citric acid, L -proline, L -erythro-4-hydroxyglutamate, N -methylhydantoin, N -carbamoylputrescine, spermidine, and 5-aminopentanoic acid were reduced significantly; compared with those in the NADKD group, the levels of linoleic acid, γ-linolenic acid, and L -malic acid in the ADKD group were increased significantly ( P < 0.05), while the levels of L -proline, L -erythro-4-hydroxyglutamate, N -carbamoylputrescine, and spermidine were significantly reduced ( P < 0.05). However, there were no significant difference between the SDM group and NADKD group ( P > 0.05). Conclusion The urine metabolomic profiles between the NADKD group and the ADKD group are significantly different. Specifically, these two groups have distinct levels of linoleic acid, γ-linolenic acid, L -malic acid, L -proline, L -erythro-4-hydroxyglutamate, N -carbamoylputrescine, and spermidine.