Drug resistance‐related microRNAs in osteosarcoma: Translating basic evidence into therapeutic strategies

Although the application of multiple chemotherapy brought revolutionary changes to improve overall survival of osteosarcoma patients, the existence of multidrug resistance (MDR) has become a great challenge for successful osteosarcoma treatment in recent decades. Substantial studies have revealed various underlying mechanisms of MDR in cancers. As for osteosarcoma, evidence has highlighted that microRNAs (miRNAs) can mediate in the processes of DNA damage response, apoptosis avoidance, autophagy induction, activation of cancer stem cells, and signal transduction. Besides, these drug resistance‐related miRNAs showed much promise for serving as candidates for predictive biomarkers of poor outcomes and shorter survival time, and therapeutic targets to reverse drug resistance and overcome treatment refractoriness. This review aims to demonstrate the potential molecular mechanisms of miRNAs‐regulated drug resistance in osteosarcoma, and provide insight in translating basic evidence into therapeutic strategies.     

MicroRNA‐351 eases insulin resistance and liver gluconeogenesis via the PI3K/AKT pathway by inhibiting FLOT2 in mice of gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is known as different degree glucose intolerance that is initially identified during pregnancy. MicroRNAs (miRs) may be a potential candidate for treatment of GDM. Herein, we suggested that miR‐351 could be an inhibitor in the progression of GDM via the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway. Microarray analysis was used to identify differentially expressed genes and predict miRs regulating flotillin 2 (FLOT2). Target relationship between miR‐351 and FLOT2 was verified. Gestational diabetes mellitus mice were treated with a series of mimic, inhibitor and small interfering RNA to explore the effect of miR‐351 on insulin resistance (IR), cell apoptosis in pancreatic tissues and liver gluconeogenesis through evaluating GDM‐related biochemical indexes, as well as expression of miR‐351, FLOT2, PI3K/AKT pathway‐, IR‐ and liver gluconeogenesis‐related genes. MiR‐351 and FLOT2 were reported to be involved in GDM. FLOT2 was the target gene of miR‐351. Gestational diabetes mellitus mice exhibited IR and liver gluconeogenesis, up‐regulated FLOT2, activated PI3K/AKT pathway and down‐regulated miR‐351 in liver tissues. Additionally, miR‐351 overexpression and FLOT2 silencing decreased the levels of FLOT2, phosphoenolpyruvate carboxykinase, glucose‐6‐phosphatase, fasting blood glucose, fasting insulin, total cholesterol, triglyceride, glyeosylated haemoglobin and homeostasis model of assessment for IR index (HOMA‐IR), extent of PI3K and AKT phosphorylation, yet increased the levels of HOMA for islet β‐cell function, HOMA for insulin sensitivity index and glucose transporter 2 expression, indicating reduced cell apoptosis in pancreatic tissues and alleviated IR and liver gluconeogenesis. Our results reveal that up‐regulation of miR‐351 protects against IR and liver gluconeogenesis by repressing the PI3K/AKT pathway through regulating FLOT2 in GDM mice, which identifies miR‐351 as a potential therapeutic target for the clinical management of GDM.     

Discovery of genomic regions and candidate genes controlling shelling percentage using QTL‐seq approach in cultivated peanut (Arachis hypogaea L.)

Cultivated peanut (Arachis hypogaea L.) is an important grain legume providing high‐quality cooking oil, rich proteins and other nutrients. Shelling percentage (SP) is the 2nd most important agronomic trait after pod yield and this trait significantly affects the economic value of peanut in the market. Deployment of diagnostic markers through genomics‐assisted breeding (GAB) can accelerate the process of developing improved varieties with enhanced SP. In this context, we deployed the QTL‐seq approach to identify genomic regions and candidate genes controlling SP in a recombinant inbred line population (Yuanza 9102 × Xuzhou 68‐4). Four libraries (two parents and two extreme bulks) were constructed and sequenced, generating 456.89–790.32 million reads and achieving 91.85%–93.18% genome coverage and 14.04–21.37 mean read depth. Comprehensive analysis of two sets of data (Yuanza 9102/two bulks and Xuzhou 68‐4/two bulks) using the QTL‐seq pipeline resulted in discovery of two overlapped genomic regions (2.75 Mb on A09 and 1.1 Mb on B02). Nine candidate genes affected by 10 SNPs with non‐synonymous effects or in UTRs were identified in these regions for SP. Cost‐effective KASP (Kompetitive Allele‐Specific PCR) markers were developed for one SNP from A09 and three SNPs from B02 chromosome. Genotyping of the mapping population with these newly developed KASP markers confirmed the major control and stable expressions of these genomic regions across five environments. The identified candidate genomic regions and genes for SP further provide opportunity for gene cloning and deployment of diagnostic markers in molecular breeding for achieving high SP in improved varieties.     

利用RNA-seq技术分析淹水胁迫下转BnERF拟南芥差异表达基因

为探究淹水胁迫下BnERF调节的耐淹防御相关途径,应用RNA-seq技术,对淹水6小时后的拟南芥(Arabidopsis thaliana)野生型(WT)和转BnERF株系(E33)幼苗进行基因表达分析。结果表明,淹水3天后,E33表现出较强的耐淹性,地上部生长状况和根系发育均明显强于野生型。E33幼苗未淹水处理时相对于野生型单独上调的基因有9个,4个为膜结合蛋白,其中2个参与MAPK级联途径,其它5个参与氧化胁迫及水分调节途径;与未淹水野生型相比,无论是未淹水处理还是淹水6小时后的E33幼苗中缺氧响应、抗氧化防护及细胞、器官发育相关基因的表达量均上调。另外,淹水6小时后E33的差异基因并未完全覆盖淹水6小时后野生型的差异基因;E33幼苗中缺氧响应、氧化胁迫响应、能量的产生与转变、乙醇代谢途径中的基因以及乙烯响应因子基因的表达量都明显高于野生型。上述结果表明,BnERF直接或间接调节植物的淹水胁迫相关生理代谢途径,参与淹水胁迫的防御过程。     

The Verticillium dahliae Sho1-MAPK pathway regulates melanin biosynthesis and is required for cotton infection

Verticillium dahliae is a soil-borne fungus that causes vascular wilt on numerous plants worldwide. The fungus survives in the soil for up to 14 years by producing melanized microsclerotia. The protective function of melanin in abiotic stresses is well documented. Here, we found that the V. dahliae tetraspan transmembrane protein VdSho1, a homolog of the Saccharomyces cerevisiae Sho1, acts as an osmosensor, and is required for plant penetration and melanin biosynthesis. The deletion mutant ΔSho1 was incubated on a cellophane membrane substrate that mimics the plant epidermis, revealing that the penetration of ΔSho1 strain was reduced compared to the wild-type strain. Furthermore, VdSho1 regulates melanin biosynthesis by a signalling mechanism requiring a kinase-kinase signalling module of Vst50-Vst11-Vst7. Strains, ΔVst50, ΔVst7 and ΔVst11 also displayed defective penetration and melanin production like the ΔSho1 strain. Defects in penetration and melanin production in ΔSho1 were restored by overexpression of Vst50, suggesting that Vst50 lies downstream of VdSho1 in the regulatory pathway governing penetration and melanin biosynthesis. Data analyses revealed that the transmembrane portion of VdSho1 was essential for both membrane penetration and melanin production. This study demonstrates that Vst50-Vst11-Vst7 module regulates VdSho1-mediated plant penetration and melanin production in V. dahliae, contributing to virulence.     

Responses to ocean acidification and diurnal temperature variation in a commercially farmed seaweed,Pyropia haitanensis (Rhodophyta)

To investigate carbon and nitrogen metabolism in Pyropia haitanensis in response to the combined conditions of ocean acidification and diurnal temperature variation, maricultured thalli were tested in acidified culture under different temperature treatments. The results showed a combined effect of ocean acidification and diurnal temperature difference on the C and N metabolism and growth of P. haitanensis. In acidifed culture, algal growth, maximum photosynthetic rate, nitrate reductase (NR) activity, amino acid (AA) content and AA score (AAS) were more significantly enhanced in seaweed under diurnal temperature variation than in seaweed at constant temperature. In acidified seawater, soluble carbohydrates in P. haitanensis increased due to greater dissolved inorganic carbon (DIC), whereas soluble proteins decreased. Under the diurnal temperature treatment, higher temperature during the light period enhanced accumulation of algal photosynthates, whereas lower temperature in the dark period reduced energy consumption, resulting in enhanced algal growth, AA content and AAS. We concluded that suitable diurnal temperature difference would be conducive to C fixation and N assimilation under ocean acidification. However, excessively high temperatures would depress algal photosynthesis and increase energy consumption, thereby exerting a negative effect on algal growth.