Background Chicken is one of the most numerous and widely distributed species around the world,and many studies support the multiple ancestral origins of domestic chickens.The research regarding the yellow skin phenot...Background Chicken is one of the most numerous and widely distributed species around the world,and many studies support the multiple ancestral origins of domestic chickens.The research regarding the yellow skin phenotype in domestic chickens(regulated by BCO2)likely originating from the grey junglefowl serves as crucial evidence for demonstrating the multiple origins of chickens.However,beyond the BCO2 gene region,much remains unknown about the introgression from the grey junglefowl into domestic chickens.Therefore,in this study,based on wholegenome data of 149 samples including 4 species of wild junglefowls and 13 local domestic chicken breeds,we explored the introgression events from the grey junglefowl to domestic chickens.Results We successfully detected introgression regions besides BCO2,including two associated with growth trait(IGFBP2 and TKT),one associated with angiogenesis(TIMP3)and two members of the heat shock protein family(HSPB2 and CRYAB).Our findings suggest that the introgression from the grey junglefowl may impact the growth performance of chickens.Furthermore,we revealed introgression events from grey junglefowl at the BCO2 region in multiple domestic chicken breeds,indicating a phenomenon where the yellow skin phenotype likely underwent strong selection and was retained.Additionally,our haplotype analysis shed light on BCO2 introgression event from different sources of grey junglefowl into domestic chickens,possibly suggesting multiple genetic flows between the grey junglefowl and domestic chickens.Conclusions In summary,our findings provide evidences of the grey junglefowl contributing to the genetic diversity of domestic chickens,laying the foundation for a deeper understanding of the genetic composition within domestic chickens,and offering new perspectives on the impact of introgression on domestic chickens.展开更多
Background: Resistance to cisplatin (DDP) leads to poor prognosis in patients with Lung Adenocarcinoma (LUAD) and limits its clinical application. It has been confirmed that autophagy promotes chemoresistance and, the...Background: Resistance to cisplatin (DDP) leads to poor prognosis in patients with Lung Adenocarcinoma (LUAD) and limits its clinical application. It has been confirmed that autophagy promotes chemoresistance and, therefore, novel strategies to reverse chemoresistance by regulating autophagy are desperately needed. Methods: The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) between A549 and A549/DDP cell lines were identified using the limma package in R, after gene expression profiles were obtained from Gene Expression Omnibus (GEO) database. By combining Autophagy-Related Genes (ARGs) from Human Autophagy Database (HADb), the interactions lncRNA-miRNAs and the interactions miRNAs-mRNAs respectively predicted by miRcode and miRDB/Targetscan database, the autophagy-related ceRNA network was constructed. Then, extraction of ceRNA subnetwork and Cox regression analyses were performed. A prognosis-related ceRNA subnetwork was constructed, and the upstream Transcription Factors (TFs) regulating lncRNAs were predicted by the JASPAR database. Finally, the expression patterns of candidate genes were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Results: A total of 3179 DEmRNAs, 180 DEmiRNAs, and 160 DElncRNAs were identified, and 35 DEmRNAs were contained in the HADb. Based on the ceRNA hypothesis, we established a ceRNA network, including 10 autophagy-related DEmRNAs, 9 DEmiRNAs, and 14 DElncRNAs. Then, LINC00520, miR-181d, and BCL2 were identified to construct a risk score model, which was confirmed to be a well-predicting prognostic factor. Furthermore, 5 TF ZNF family members were predicted to regulate LINC00520, whereas the RT-PCR results showed that the 5 ZNFs were consistent with the bioinformatics analysis. Finally, a ZNF regulatory LINC00520/miR-181d/BCL2 ceRNA subnetwork was constructed. Conclusions: An ZNFs/LINC00520/miR-181d/BCL2 axis as a novel network in DDP-resistant LUAD has been constructed successfully, which may provide potential therapeutic targets for LUAD.展开更多
Chronic pancreatitis(CP)is a major risk factor of pancreatic ductal adenocarcinoma(PDAC).How CP promotes pancreatic oncogenesis remains unclear.A characteristic feature of PDAC is its prominent desmoplasia in the tumo...Chronic pancreatitis(CP)is a major risk factor of pancreatic ductal adenocarcinoma(PDAC).How CP promotes pancreatic oncogenesis remains unclear.A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment,composed of activated fibroblasts and macrophages.Macrophages can be characterized as M1 or M2,with tumor-inhibiting or-promoting functions,respectively.We reported that Gremlin 1(GREM1),a key pro-fibrogenic factor,is upregulated in the stroma of CP.The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC.By mRNA in situ hybridization,we detected GREM1 mRNA expression withinα-smooth muscle actin(SMA)-positive fibroblasts of the pancreatic stroma.These designated FibroblastsGrem1+marginally increased from CP to pancreatic intraepithelial neoplasia(PanIN)and PDAC.Within PDAC,FibroblastsGrem1+increased with higher pathological tumor stages and in a majority of PDAC subtypes screened.Additionally,FibroblastsGrem1+positively correlated with total macrophages(MacCD68+)and M2 macrophages(M2CD163+)in PDAC.To begin exploring potential molecular links between FibroblastsGrem1+and macrophages in PDAC,we examined the expression of macrophage migration inhibitory factor(MIF),an endogenous counteracting molecule of GREM1 and an M1 macrophage promoting factor.By IHC staining of MIF,we found MIF to be expressed by tumor cells,positively correlated with GREM1;by IHC co-staining,we found MIF to be negatively correlated with M2CD163+expression.Our findings suggest that GREM1 expression by activated fibroblasts may promote PDAC development,and GREM1/MIF may play an important role in macrophage phenotype.展开更多
基金supported by the earmarked fund for the Beijing Agriculture Innovation Consortium(BAIC06-2023-G01)open project of Xinjiang Production&Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin(BRZD2104)Fuyang Normal University Provincial and Ministerial Open Platform Fund(FSKFKT026D).
文摘Background Chicken is one of the most numerous and widely distributed species around the world,and many studies support the multiple ancestral origins of domestic chickens.The research regarding the yellow skin phenotype in domestic chickens(regulated by BCO2)likely originating from the grey junglefowl serves as crucial evidence for demonstrating the multiple origins of chickens.However,beyond the BCO2 gene region,much remains unknown about the introgression from the grey junglefowl into domestic chickens.Therefore,in this study,based on wholegenome data of 149 samples including 4 species of wild junglefowls and 13 local domestic chicken breeds,we explored the introgression events from the grey junglefowl to domestic chickens.Results We successfully detected introgression regions besides BCO2,including two associated with growth trait(IGFBP2 and TKT),one associated with angiogenesis(TIMP3)and two members of the heat shock protein family(HSPB2 and CRYAB).Our findings suggest that the introgression from the grey junglefowl may impact the growth performance of chickens.Furthermore,we revealed introgression events from grey junglefowl at the BCO2 region in multiple domestic chicken breeds,indicating a phenomenon where the yellow skin phenotype likely underwent strong selection and was retained.Additionally,our haplotype analysis shed light on BCO2 introgression event from different sources of grey junglefowl into domestic chickens,possibly suggesting multiple genetic flows between the grey junglefowl and domestic chickens.Conclusions In summary,our findings provide evidences of the grey junglefowl contributing to the genetic diversity of domestic chickens,laying the foundation for a deeper understanding of the genetic composition within domestic chickens,and offering new perspectives on the impact of introgression on domestic chickens.
文摘Background: Resistance to cisplatin (DDP) leads to poor prognosis in patients with Lung Adenocarcinoma (LUAD) and limits its clinical application. It has been confirmed that autophagy promotes chemoresistance and, therefore, novel strategies to reverse chemoresistance by regulating autophagy are desperately needed. Methods: The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) between A549 and A549/DDP cell lines were identified using the limma package in R, after gene expression profiles were obtained from Gene Expression Omnibus (GEO) database. By combining Autophagy-Related Genes (ARGs) from Human Autophagy Database (HADb), the interactions lncRNA-miRNAs and the interactions miRNAs-mRNAs respectively predicted by miRcode and miRDB/Targetscan database, the autophagy-related ceRNA network was constructed. Then, extraction of ceRNA subnetwork and Cox regression analyses were performed. A prognosis-related ceRNA subnetwork was constructed, and the upstream Transcription Factors (TFs) regulating lncRNAs were predicted by the JASPAR database. Finally, the expression patterns of candidate genes were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Results: A total of 3179 DEmRNAs, 180 DEmiRNAs, and 160 DElncRNAs were identified, and 35 DEmRNAs were contained in the HADb. Based on the ceRNA hypothesis, we established a ceRNA network, including 10 autophagy-related DEmRNAs, 9 DEmiRNAs, and 14 DElncRNAs. Then, LINC00520, miR-181d, and BCL2 were identified to construct a risk score model, which was confirmed to be a well-predicting prognostic factor. Furthermore, 5 TF ZNF family members were predicted to regulate LINC00520, whereas the RT-PCR results showed that the 5 ZNFs were consistent with the bioinformatics analysis. Finally, a ZNF regulatory LINC00520/miR-181d/BCL2 ceRNA subnetwork was constructed. Conclusions: An ZNFs/LINC00520/miR-181d/BCL2 axis as a novel network in DDP-resistant LUAD has been constructed successfully, which may provide potential therapeutic targets for LUAD.
基金This study was supported by the National Institutes of Health grant 1 R21 AA027014-01A1(T.C.K.)。
文摘Chronic pancreatitis(CP)is a major risk factor of pancreatic ductal adenocarcinoma(PDAC).How CP promotes pancreatic oncogenesis remains unclear.A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment,composed of activated fibroblasts and macrophages.Macrophages can be characterized as M1 or M2,with tumor-inhibiting or-promoting functions,respectively.We reported that Gremlin 1(GREM1),a key pro-fibrogenic factor,is upregulated in the stroma of CP.The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC.By mRNA in situ hybridization,we detected GREM1 mRNA expression withinα-smooth muscle actin(SMA)-positive fibroblasts of the pancreatic stroma.These designated FibroblastsGrem1+marginally increased from CP to pancreatic intraepithelial neoplasia(PanIN)and PDAC.Within PDAC,FibroblastsGrem1+increased with higher pathological tumor stages and in a majority of PDAC subtypes screened.Additionally,FibroblastsGrem1+positively correlated with total macrophages(MacCD68+)and M2 macrophages(M2CD163+)in PDAC.To begin exploring potential molecular links between FibroblastsGrem1+and macrophages in PDAC,we examined the expression of macrophage migration inhibitory factor(MIF),an endogenous counteracting molecule of GREM1 and an M1 macrophage promoting factor.By IHC staining of MIF,we found MIF to be expressed by tumor cells,positively correlated with GREM1;by IHC co-staining,we found MIF to be negatively correlated with M2CD163+expression.Our findings suggest that GREM1 expression by activated fibroblasts may promote PDAC development,and GREM1/MIF may play an important role in macrophage phenotype.