RPA3(Replication Protein A3)(14 kD)is a part of the canonical heterotrimeric replication protein A complex(RPA/RP-A).This study aimed to explore the functional role of RPA3 and the mechanisms of its dysregulation in b...RPA3(Replication Protein A3)(14 kD)is a part of the canonical heterotrimeric replication protein A complex(RPA/RP-A).This study aimed to explore the functional role of RPA3 and the mechanisms of its dysregulation in breast cancer.Data from the Cancer Genome Atlas(TCGA)-breast cancer patients and GSE75688 were utilized for gene expression and survival analysis.Breast cancer cell lines MDA-MB-231 and SK-BR-3 were used for in-vitro cell studies.Clonogenic assay and immunofluorescent staining ofγ-H2AX were performed to examine radiation-induced cytotoxicity.Systemic correlation analysis was performed to identify potential transcription factors(TFs)regulating RPA3 expression.ChIP-qPCR and dual-luciferase assay were conducted to verify the transcriptional activating effect of YY1 on RPA3 expression.Bioinformatic analysis showed that RPA3 expression was upregulated in breast cancer.Its upregulation was associated with poor survival of basal-like and HER2+cases.RPA3 inhibition by siRNA reduced colony formation and increasedγ-H2AX foci formation after irradiation in MDA-MB-231 and SK-BR-3 cells.RPA3 expression was transcriptionally activated by YY1 via promoter binding in the two cell lines.Both RPA3 and YY1 expression were positively correlated with their gene-level copy numbers.RPA3 might serve as a potential target for radio-sensitization in basal-like and HER2+breast cancer.展开更多
The sensitivity of Chinese soybean cultivars to ambient ozone（O3） in the field is unknown,although soybean is a major staple food in China. Using ethylenediurea（EDU） as an O3 protectant, we tested the gas exchange...The sensitivity of Chinese soybean cultivars to ambient ozone（O3） in the field is unknown,although soybean is a major staple food in China. Using ethylenediurea（EDU） as an O3 protectant, we tested the gas exchange, pigments, antioxidants and biomass of 19 cultivars exposed to 28 ppm·hr AOT40（accumulated O3 over an hourly concentration threshold of40 ppb） over the growing season at a field site in China. By comparing the average biomass with and without EDU, we estimated the cultivar-specific sensitivity to O3 and ranked the cultivars from very tolerant（〈 10% change） to highly sensitive（〉 45% change）, which helps in choosing the best-suited cultivars for local cultivation. Higher lipid peroxidation and activity of the ascorbate peroxidase enzyme were major responses to O3 damage, which eventually translated into lower biomass production. The constitutional level of total ascorbate in the leaves was the most important parameter explaining O3 sensitivity among these cultivars. Surprisingly, the role of stomatal conductance was insignificant. These results will guide future breeding efforts towards more O3-tolerant cultivars in China, while strategies for implementing control measures of regional O3 pollution are being implemented. Overall, these results suggest that present ambient O3 pollution is a serious concern for soybean in China, which highlights the urgent need for policy-making actions to protect this critical staple food.展开更多
文摘RPA3(Replication Protein A3)(14 kD)is a part of the canonical heterotrimeric replication protein A complex(RPA/RP-A).This study aimed to explore the functional role of RPA3 and the mechanisms of its dysregulation in breast cancer.Data from the Cancer Genome Atlas(TCGA)-breast cancer patients and GSE75688 were utilized for gene expression and survival analysis.Breast cancer cell lines MDA-MB-231 and SK-BR-3 were used for in-vitro cell studies.Clonogenic assay and immunofluorescent staining ofγ-H2AX were performed to examine radiation-induced cytotoxicity.Systemic correlation analysis was performed to identify potential transcription factors(TFs)regulating RPA3 expression.ChIP-qPCR and dual-luciferase assay were conducted to verify the transcriptional activating effect of YY1 on RPA3 expression.Bioinformatic analysis showed that RPA3 expression was upregulated in breast cancer.Its upregulation was associated with poor survival of basal-like and HER2+cases.RPA3 inhibition by siRNA reduced colony formation and increasedγ-H2AX foci formation after irradiation in MDA-MB-231 and SK-BR-3 cells.RPA3 expression was transcriptionally activated by YY1 via promoter binding in the two cell lines.Both RPA3 and YY1 expression were positively correlated with their gene-level copy numbers.RPA3 might serve as a potential target for radio-sensitization in basal-like and HER2+breast cancer.
基金supported by State Key Laboratory of Soil and Sustainable Agriculture(No.Y20160030)the Hundred Talents Program,Chinese Academy of Sciences,Chinese Academy of Sciences President's International Fellowship Initiative(PIFI)for Senior Scientists(Grant Number 2016VBA057)CNR-CAS bilateral agreement 2017–2019(Ozone impacts on plant ecosystems in China and Italy)
文摘The sensitivity of Chinese soybean cultivars to ambient ozone（O3） in the field is unknown,although soybean is a major staple food in China. Using ethylenediurea（EDU） as an O3 protectant, we tested the gas exchange, pigments, antioxidants and biomass of 19 cultivars exposed to 28 ppm·hr AOT40（accumulated O3 over an hourly concentration threshold of40 ppb） over the growing season at a field site in China. By comparing the average biomass with and without EDU, we estimated the cultivar-specific sensitivity to O3 and ranked the cultivars from very tolerant（〈 10% change） to highly sensitive（〉 45% change）, which helps in choosing the best-suited cultivars for local cultivation. Higher lipid peroxidation and activity of the ascorbate peroxidase enzyme were major responses to O3 damage, which eventually translated into lower biomass production. The constitutional level of total ascorbate in the leaves was the most important parameter explaining O3 sensitivity among these cultivars. Surprisingly, the role of stomatal conductance was insignificant. These results will guide future breeding efforts towards more O3-tolerant cultivars in China, while strategies for implementing control measures of regional O3 pollution are being implemented. Overall, these results suggest that present ambient O3 pollution is a serious concern for soybean in China, which highlights the urgent need for policy-making actions to protect this critical staple food.
