Schisandrin B suppresses gastric cancer cell growth and enhances the efficacy of chemotherapy drug 5-FU in vitro and in vivo.

Gastric cancer (GC) is a serious affliction worldwide and remains to be the fourth most common cancer with poor prognosis, especially in advanced stage. Chemotherapy is one of the main therapeutic means. The purpose of this study was to investigate the antitumor effects of Schisandrin B (Sch B) on GC cells both in vitro and in vivo, as well as the synergistic effect with 5-fluorouracil (5-FU), and to preliminarily explore the relevant mechanism of action. Our results showed that Sch B inhibited the growth, migration and invasion of GC cells. Besides, Sch B could effectively inhibit the phosphorylation of STAT3 (signal transducer and activator of transcription 3), induce autophagy, and enhance the efficacy of chemotherapy drug 5-FU in vitro and in vivo. Taken together, the findings indicate that Sch B displays potent antitumor activities. The co-administration of Sch B and 5-FU might be a promising way for future therapy of GC.

C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression.

BACKGROUND: Growing evidence shows that long non-coding RNAs (lncRNAs) play significant roles in cancer development. However, the functions of most lncRNAs in human gastric cancer are still not fully understood. Here, we explored the role of a novel c-Myc-activated lncRNA, LINC01050, in gastric cancer progression. METHODS: The expression of LINC01050 in the context of gastric cancer was assessed using The Cancer Genome Atlas datasets. Its functions in gastric cancer were investigated through gain- and loss-of-function experiments combined with the Cell Counting Kit-8 assays, colony-forming assays, Transwell assays, flow cytometry, Western blot analyses, and xenograft tumor and mouse metastasis models. Potential LINC01050 transcription activators were screened via bioinformatics and validated by chromatin immunoprecipitation and luciferase assays. The interaction between LINC01050 and miR-7161-3p and the targets of miR-7161-3p were predicted by bioinformatics analysis and confirmed by a luciferase assay, RNA immunoprecipitation, RNA pull-down, and rescue experiments. RESULTS: LINC01050 was significantly up-regulated in gastric cancer, and its high expression was positively correlated with a poor prognosis. The transcription factor c-Myc was found to directly bind to the LINC01050 promoter region and activate its transcription. Furthermore, overexpression of LINC01050 was confirmed to promote gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. At the same time, its knockdown inhibited gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro along with tumor growth and metastasis in vivo. Moreover, mechanistic investigations revealed that LINC01050 functions as a molecular sponge to absorb cytosolic miR-7161-3p, which reduces the miR-7161-3p-mediated translational repression of SPZ1, thus contributing to gastric cancer progression. CONCLUSIONS: Taken together, our results identified a novel gastric cancer-associated lncRNA, LINC01050, which is activated by c-Myc. LINC01050 may be considered a potential therapeutic target for gastric cancer.

Downregulation of LINC01021 by curcumin analog Da0324 inhibits gastric cancer progression through activation of P53.

Curcumin is a safe, cost-effective natural agent with multiple targets that displays therapeutic potential in cancer. Recently, we reported a novel curcumin analog, Da0324, which exhibited significantly improved stability and anti-cancer activity. However, the molecular mechanism underlying the anti-cancer activity of Da0324 remains largely unknown. Long non-coding RNAs have been shown to play important roles in cancer development and progression and may be potential targets for cancer therapy. Here, we showed that Da0324 treatment down-regulated the expression of LINC01021 in gastric cancer cells. Da0324 treatment or knockdown of LINC01021 by antisense oligos significantly inhibited gastric cancer cell growth, and also up-regulated P53 expression and down-regulated Bcl-2 expression in vitro and in vivo. Furthermore, Da0324 treatment or knockdown of LINC01021 in gastric cancer cells suppressed cell migration, invasion and epithelial-mesenchymal transition (EMT), as well as induced apoptosis and autophagy. In addition, overexpression of LINC01021 promoted growth and EMT, inhibited P53 expression and increased Bcl-2 expression in gastric cancer cells. Finally, overexpression of LINC01021 reversed the anti-cancer effect of Da0324. Our findings indicate a novel anti-cancer mechanism for Da0324, and that LINC01021 might be a potential therapeutic target for the treatment of gastric cancer.

The value of the atherogenic index of plasma in non-obese people with non-alcoholic fatty liver disease: a secondary analysis based on a cross-sectional study.

BACKGROUND AND OBJECTIVES: The atherogenic index of plasma (AIP) is elevated in fatty liver disease, but its value in non-obese people with non-alcoholic fatty liver disease (NAFLD) is unclear. This study aimed to investigate the relationship between AIP and NAFLD as well as to determine whether AIP might be used as an indicator of NAFLD in non-obese individuals. METHODS: The present study involved non-obese Chinese and Japanese participants. Risk factors are evaluated using univariate and multivariate analysis. The performance of risk factors was compared according to the area under the receiver operating characteristic curve. RESULTS: In the unadjusted model, the odds ratio (OR) for every 1 standard deviation (SD) increase in AIP was 52.30. In adjusted models I and II, the OR for every 1 SD increase in AIP was 36.57 and 50.84, respectively. The area under the receiver operating characteristic curve for AIP was 0.803 and 0.802 in the development and validation groups, respectively. The best cut-off value of AIP for discrimination between NAFLD and non-NAFLD was 0.005 in the Chinese group and - 0.220 in the Japanese group. CONCLUSIONS: AIP and NAFLD are positively correlated in Chinese and Japanese populations. Therefore, AIP can be used as a new screening indicator for non-obese people with NAFLD in different nations.

Hypoxia induces the activation of hepatic stellate cells through the PVT1-miR-152-ATG14 signaling pathway.

Increasing studies have indicated that hypoxia serves as a pivotal microenvironmental factor that facilitates activation of hepatic stellate cells (HSCs). However, the mechanism by which hypoxia activates HSCs is not clear. Here, we demonstrated that plasmacytoma variant translocation 1 (PVT1) and autophagy were overexpressed in liver fibrotic specimens. In primary mouse HSCs, both PVT1 and autophagy were induced by hypoxia. Further study showed that hypoxia-induced autophagy depended on expression of PVT1 and miR-152 in HSCs. Luciferase reporter assay indicated that autophagy-related gene 14 (ATG14) was a direct target of miR-152. In addition, inhibition of autophagy by 3-methyladenine and Beclin-1 siRNA impeded activation of HSCs cultured in 1% O2. Taken together, autophagy induction via the PVT1-miR-152-ATG14 signaling pathway contributes to activation of HSCs under hypoxia condition.

Screening and verifying key genes with poor prognosis in colon cancer through bioinformatics analysis.

BACKGROUND: Colon cancer (CC) is one of the tumors with high morbidity and mortality in the world, and has a trend of younger generation. The molecular level of CC has not been fully elaborated. The purpose of this study is to screen and identify important genes with poor prognosis and their mechanisms at different levels. METHODS: GSE74602 and GSE10972 gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. There were 58 normal tissues and 58 CC tissues. Differentially expressed genes (DEGs) were screened out by using the GEO2R tool and Venn diagram. Then, the DAVID online database was used to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Six hub genes with the highest correlation were screened out after the modular analysis of the protein-protein interaction (PPI) network by using Cytoscape's MCODE plug-in. Finally, the overall survival of key hub genes and potential pathways were verified in GEPIA and UALCAN database. RESULTS: A total of 78 up-regulated DEGs were enriched in the mitotic nuclear division, cell division, cell proliferation, anaphase-promoting complex-dependent catabolic process and G2/M transition of the mitotic cell cycle. In total, 130 down-regulated DEGs were enriched in muscle contraction, bicarbonate transport, cellular response to zinc ion, negative regulation of growth, negative regulation of leukocyte apoptotic process and one-carbon metabolic process. CDK1, CCNB1, CDC20, AURKA, CCNA2 and TOP2A were the top six hub genes, mainly enriched in cell cycle pathways. Among them, CCNB1, CDK1, CDC20, CCNA2 were enriched in the G2/M phase. GEPIA and UALCAN database confirmed that CCNA2 and CCNB1 had a significant relationship with the poor prognosis of CC patients. Meanwhile, there was a positive correlation between the two. CONCLUSIONS: Screening out genes with abnormal expression in CC help understand the initiation and progression of CC at the molecular level and explore candidate biomarkers for diagnosis, treatment and prognosis.