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Abstract Background The levels of soluble sugars, such as glucose and sucrose, help regulate many plant metabolic, physiological and developmental processes. Genetic screens are helping identify some of the loci involved in plant sugar response and reveal extensive cross-talk between sugar and phytohormone response pathways. Results A forward genetic screen was performed to identify mutants with increased resistance to the inhibitory effects of high levels of exogenous sugars on early Arabidopsis seedling development. The positional cloning and characterization of two of these sugar insensitive (sis) mutants, both of which are also involved in abscisic acid (ABA) biosynthesis or response, are reported. Plants carrying mutations in SIS7/NCED3/STO1 or SIS10/ABI3 are resistant to the inhibitory effects of high levels of exogenous Glc and Suc. Quantitative RT-PCR analyses indicate transcriptional upregulation of ABA biosynthesis genes by high concentrations of Glc in wild-type germinating seeds. Gene expression profiling revealed that a significant number of genes that are expressed at lower levels in germinating sis7-1/nced3-4/sto1-4 seeds than in wild-type seeds are implicated in auxin biosynthesis or transport, suggesting cross-talk between ABA and auxin response pathways. The degree of sugar insensitivity of different sis10/abi3 mutant seedlings shows a strong positive correlation with their level of ABA insensitivity during seed germination. Conclusion Mutations in the SIS7/NCED3/STO1 gene, which is primarily required for ABA biosynthesis under drought conditions, confer a sugar-insensitive phenotype, indicating that a constitutive role in ABA biosynthesis is not necessary to confer sugar insensitivity. Findings presented here clearly demonstrate that mutations in ABI3 can confer a sugar-insensitive phenotype and help explain previous, mixed reports on this topic by showing that ABA and sugar insensitivity exhibit a strong positive correlation in different abi3 mutants. Expression profiling revealed a potentially novel regulation of auxin metabolism and transport in an ABA deficient mutant, sis7-1/nced3-4/sto1-4.

MicroRNAs (miRNAs) are involved in the pathogenesis of diverse types of malignancies, including hepatocellular carcinoma (HCC). However, miR-365 has rarely been reported in HCC. The purpose of the current study was to identify the clinical relevance of miR-365 in HCC and examine the potential downstream signaling effectors.Using real-time RT-qPCR, we confirmed that miR-365 expression was markedly decreased in HCC tissues (3.5138 ± 2.2527) compared to that in paraneoplastic liver tissues (6.5950 ± 4.1230, P<0.001). Receiver operating characteristic curves to assess the diagnostic value of miR-365 in HCC demonstrated that the area under the curve was 0.757. Furthermore, down-regulation of miR-365 was remarkably correlated to the number of tumor nodes, status of metastasis, clinical TNM stage, portal vein tumor embolus and vaso-invasion. In addition to the clinical value of miR-365, a total of 238 downstream direct targets selected by online predictive algorithms and key genes generated from natural language processing and the Cancer Genome Atlas (TCGA) were pooled for bioinformatics analysis. These potential targets were mainly enriched in the Ras Pathway using PANTHER analysis and the 'Pathways in Cancer' using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In conclusion, down-regulated miR-365 may contribute to the progression and metastasis of HCC via targeting multiple signaling pathways, and miR-365 may act as a novel biomarker for HCC., Competing Interests: None., (IJCEP Copyright © 2017.)

Background: MiR-101-3p has been reported to suppress invasion and metastasis in hepatocellular carcinoma (HCC) cells. However, the relevant mechanisms are still unclear. The research seeks to determine systematic value of miR-101-3p in HCC, and comprehensively summarize the predicted target genes as well as their potential function, pathways and networks in HCC., Methods: The miR-101-1 profiles in 353 HCC patients from The Cancer Genome Atlas (TCGA) were analyzed. Meta-analysis was performed to estimate relationship of miR-101 (including precursor and mature miR-101) with clinical features and prognosis in HCC. Further, the promising targets of miR-101-3p were predicted and followed with Gene Ontology (GO), pathway and network analysis. In addition, the functional impact of miR-101-3p was confirmed with in vitro experiments in HCC cells., Results: In TCGA data, low-expression of miR-101-1 might be a diagnostic (AUC: 0.924, 95% CI: 0.894-0.953) and prognostic (HR=1.55) marker for HCC. Down-regulated miR-101-1 also correlated with poor differentiation, advanced TNM stage, lymph node metastasis and high AFP level of HCC. Meta-analysis revealed that miR-101 down-regulation were associated with poor prognosis, high AFP level and advanced TNM stage of HCC. Moreover, 343 hub genes were filtered and miR-101-3p may be involved in intracellular signaling cascade, transcription, metabolism and cell proliferation. Focal adhesion and pathways in cancer were also significantly enriched. In vitro experiments demonstrated that miR-101-3p inhibited proliferation and promoted apoptosis in HCC cells., Conclusions: MiR-101-1 may be a prospective biomarker for diagnosis and prognosis of HCC. Potential targets of miR-101-3p could regulate genesis and development of HCC. The data offers insights into biological significances and promising targets of miR-101-3p for further investigation and potential therapies in HCC., Competing Interests: None.