Hypoxia inducible factor-1alpha (HIF-1alpha) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1alpha was found in 37 of the 72 (51.39%) tumor specimens, and significantly correlated with venous invasion and lymphonode invasion. Patients with high expression of HIF-1alpha had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1alpha expression was a borderline independent factor of overall survival. HIF-1alpha expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1alpha protein expression in vitro. These results suggested that HIF-1alpha, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients.
ORCID IDs: 0000-0002-0738-7899 (M.Z.); 0000-0002-2121-9517 (M.C.).In many higher plants, seed oil accumulation is precisely controlled by intricate multilevel regulatory networks, among which transcriptional regulation mainly influences oil biosynthesis. In Arabidopsis (Arabidopsis thaliana), the master positive transcription factors, WRINKLED1 (WRI1) and LEAFY COTYLEDON1-LIKE (L1L), are important for seed oil accumulation. We found that an R2R3-MYB transcription factor, MYB89, was expressed predominantly in developing seeds during maturation. Oil and major fatty acid biosynthesis in seeds was significantly promoted by myb89-1 mutation and MYB89 knockdown; thus, MYB89 was an important repressor during seed oil accumulation. RNA sequencing revealed remarkable up-regulation of numerous genes involved in seed oil accumulation in myb89 seeds at 12 d after pollination. Posttranslational activation of a MYB89-glucocorticoid receptor fusion protein and chromatin immunoprecipitation assays demonstrated that MYB89 inhibited seed oil accumulation by directly repressing WRI1 and five key genes and by indirectly suppressing L1L and 11 key genes involved in oil biosynthesis during seed maturation. These results help us to understand the novel function of MYB89 and provide new insights into the regulatory network of transcriptional factors controlling seed oil accumulation in Arabidopsis.
BackgroundGrowing evidence has implicated the important role of the long non-coding RNAs (lncRNAs) in gastric cancer progression. In this study, we examined the expression of lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in gastric cancer tissues and elucidated the molecular mechanisms underlying ZEB2-AS1-mediated gastric cancer progression.MethodsQuantitative real-time PCR measured the gene expression level; CCK-8, colony formation and cell invasion assays determined gastric cancer cell proliferation, growth and invasion, respectively; the xenograft nude mice model was used to determine in vivo tumor growth; Bioinformatics analysis and luciferase reporter assay determined the downstream targets of ZEB2-AS1 and miR-143-5p. The expression of ZEB2-AS1 was upregulated in gastric cancer cell lines.ResultsKnockdown of ZEB2-AS1 suppressed gastric cancer cell proliferation, growth and invasion, and also suppressed in vivo tumor growth in the nude mice. Overexpression of ZEB2-AS1 potentiated gastric cancer cell proliferation, growth and invasion. Bioinformatics analysis and luciferase reporter assay showed that miR-143-5p was a direct target of ZEB2-AS1 and was negatively regulated by ZEB2-AS1. Furthermore, hypoxia-inducible factor-1α (HIF-1α) was found to be a target of miR-143-5p and was negatively regulated by miR-143-5p. The rescue in vitro assays showed that the effects of ZEB2-AS1 overexpression on gastric cancer cell proliferation, growth and invasion was mediated via miR-143-5p/HIF-1α. ZEB2-AS1 and HIF-1α was upregulated in gastric cancer tissues, while miR-143-5p was down-regulated; and ZEB2-AS1 expression level was inversely correlated with miR-143-5p expression level, and positively correlated with HIF-1α mRNA expression level; while miR-143-5p expression level was inversely correlated with HIF-1α expression level. High ZEB2-AS1 expression level was correlated with poor differentiation, lymph node metastasis and distant metastasis.ConclusionCollectively, our results indicated that ZEB2-AS1 was up-regulated in gastric cancer tissues and cells and promoted cell proliferation and metastasis through miR-143-5p/HIF-1α pathway, which may provide a promising target for treatment of gastric cancer.
The MYB family of transcription factors is important in regulatory networks controlling development, metabolism and responses to biotic and abiotic stresses in Arabidopsis. However, their role in regulating fatty acid accumulation in seeds is still largely unclear. Here, we found that MYB76, localized in the nucleus, was predominantly expressed in developing seeds during maturation. The myb76 mutation caused a significant increase in the amounts of total fatty acids and several major fatty acid compositions in mature seeds, suggesting that MYB76 functioned as an important repressor during seed oil biosynthesis. RNA sequencing and quantitative real-time PCR analysis revealed remarkable alteration of numerous genes involved in photosynthesis, fatty acid biosynthesis, modification, and degradation, and oil body formation in myb76 seeds at 12 days after pollination. These results help us to understand the novel function of MYB76 and provide new insights into the regulatory network of MYB transcriptional factors controlling seed oil accumulation in Arabidopsis.
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