cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19152631
title: Acetylshikonin suppresses diffuse large B-Cell Lymphoma cell growth by targeting the T-lymphokine-activated killer cell-originated protein kinase signalling pathway

description: Diffuse large B-cell lymphoma (DLBCL) is one of the most common causes of cancer death worldwide, and responds poorly to the existing treatments. Thus, identifying novel therapeutic targets of DLBCL is urgently needed. In this study, we found that T-lymphokine-activated killer cell-originated protein kinase (TOPK) was highly expressed in DLBCL cells and tissues. Data from the GEPIA database also indicated that TOPK was highly expressed in DLBCL tissues. The high expression levels of proteins were identified via Western blots and immunohistochemistry (IHC). TOPK knockdown inhibited cell growth and induced apoptosis of DLBCL cells with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium (MTS) and flow cytometry. Further experiments demonstrated that acetylshikonin, a compound that targeted TOPK, could attenuate cell growth and aggravate cell apoptosis through TOPK/extracellular signal-regulated kinase (ERK)-1/2 signaling, as shown by MTS, flow cytometry and Western blots. In addition, we demonstrated that TOPK modulated the effect of acetylshikonin on cell proliferation and apoptosis in U2932 and OCI-LY8 cells using MTS, flow cytometry and Western blots. Taken together, the present study suggests that acetylshikonin suppresses the growth of DLBCL cells by attenuating TOPK signaling, and the targeted inhibition of TOPK by acetylshikonin may be a promising approach for the treatment of DLBCL.
DOI: 10.6084/m9.figshare.19152631.v1
title: Acetylshikonin suppresses diffuse large B-Cell Lymphoma cell growth by targeting the T-lymphokine-activated killer cell-originated protein kinase signalling pathway

description: Diffuse large B-cell lymphoma (DLBCL) is one of the most common causes of cancer death worldwide, and responds poorly to the existing treatments. Thus, identifying novel therapeutic targets of DLBCL is urgently needed. In this study, we found that T-lymphokine-activated killer cell-originated protein kinase (TOPK) was highly expressed in DLBCL cells and tissues. Data from the GEPIA database also indicated that TOPK was highly expressed in DLBCL tissues. The high expression levels of proteins were identified via Western blots and immunohistochemistry (IHC). TOPK knockdown inhibited cell growth and induced apoptosis of DLBCL cells with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium (MTS) and flow cytometry. Further experiments demonstrated that acetylshikonin, a compound that targeted TOPK, could attenuate cell growth and aggravate cell apoptosis through TOPK/extracellular signal-regulated kinase (ERK)-1/2 signaling, as shown by MTS, flow cytometry and Western blots. In addition, we demonstrated that TOPK modulated the effect of acetylshikonin on cell proliferation and apoptosis in U2932 and OCI-LY8 cells using MTS, flow cytometry and Western blots. Taken together, the present study suggests that acetylshikonin suppresses the growth of DLBCL cells by attenuating TOPK signaling, and the targeted inhibition of TOPK by acetylshikonin may be a promising approach for the treatment of DLBCL.
DOI: 10.6084/m9.figshare.18865360
title: Tandem mass tag-based serum proteomic profiling revealed diabetic foot ulcer pathogenesis and potential therapeutic targets

description: Diabetic foot ulcer (DFU), one of the most serious complications of diabetes mellitus, is associated with a high amputation rate and decreased life quality. The impact of blood serum proteins on the occurrence and development of DFU has attracted a lot of interest. In this study, we aimed to define and compare the serum proteome of patients with DFU and healthy control (HC) to provide new insights into DFU pathogenesis. DFU patients and age- and sex-matched HCs were enrolled in this study (n = 54). We screened alterations in blood serum proteins from DFU patients and HC using a tandem mass tag (TMT) method based on liquid chromatography-mass spectrometry (LC-MS/MS) quantitative proteomics, and the differentially expressed proteins (DEPs) were further validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). A total of 173 DEPs (100 up-regulated and 73 down-regulated) were identified between the DFU and HC groups (<i>P</i> &lt; 0.05). Proteomic and bioinformatics analyses indicated that the proteins in the DFU group were mainly related to extracellular matrix (ECM)-receptor interaction and complement and coagulation cascades. The up-regulated DEPs were further verified by PRM and ELISA. LRG1, CD5L, CRP, IGHA1, and LBP were proved upregulated in DFU and these proteins are mainly related to immune response and complement activation. Our findings help to provide a more comprehensive understanding of the pathogenesis of DFU and new insight into potential therapeutic targets.
DOI: 10.6084/m9.figshare.18865360.v1
title: Tandem mass tag-based serum proteomic profiling revealed diabetic foot ulcer pathogenesis and potential therapeutic targets

description: Diabetic foot ulcer (DFU), one of the most serious complications of diabetes mellitus, is associated with a high amputation rate and decreased life quality. The impact of blood serum proteins on the occurrence and development of DFU has attracted a lot of interest. In this study, we aimed to define and compare the serum proteome of patients with DFU and healthy control (HC) to provide new insights into DFU pathogenesis. DFU patients and age- and sex-matched HCs were enrolled in this study (n = 54). We screened alterations in blood serum proteins from DFU patients and HC using a tandem mass tag (TMT) method based on liquid chromatography-mass spectrometry (LC-MS/MS) quantitative proteomics, and the differentially expressed proteins (DEPs) were further validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). A total of 173 DEPs (100 up-regulated and 73 down-regulated) were identified between the DFU and HC groups (<i>P</i> &lt; 0.05). Proteomic and bioinformatics analyses indicated that the proteins in the DFU group were mainly related to extracellular matrix (ECM)-receptor interaction and complement and coagulation cascades. The up-regulated DEPs were further verified by PRM and ELISA. LRG1, CD5L, CRP, IGHA1, and LBP were proved upregulated in DFU and these proteins are mainly related to immune response and complement activation. Our findings help to provide a more comprehensive understanding of the pathogenesis of DFU and new insight into potential therapeutic targets.
DOI: 10.6084/m9.figshare.18126265
title: Integrated bioinformatics and experiments reveal the roles and driving forces for HSF1 in colorectal cancer

description: Heat shock factor 1 (HSF1) has watershed significance in different tumors. However, the roles and driving forces for HSF1 in colorectal cancer (CRC) are poorly understood. Our study integrally analyzed the roles and driving forces for HSF1 in CRC by bioinformatics and experiments. The expression and prognostic characteristics of HSF1 were analyzed via UALCAN, GEPIA2, TISIDB, Prognoscan and HPA databases. Then, we analyzed the correlation between HSF1 expression and immune features via TIMER2 database. Subsequently, we explored the driving forces for HSF1 abnormal expression in CRC by bioinformatics and experiments. Our results showed that HSF1 was overexpressed and correlated with poor prognosis in CRC. And the expression of HSF1 was significantly correlated with multiple immune cell infiltration and was negatively correlated with immunomodulators such as programmed cell death 1 ligand 1(PD-L1). Along with many driver genes in particular <i>TP53</i>, super-enhancer, miRNA and DNA methylation were all responsible for HSF1 overexpression in CRC. Moreover, we demonstrated that β-catenin could promote the translation process of HSF1 mRNA by interacting with HuR, which could directly bind to the coding sequence (CDS) region of HSF1 mRNA. Collectively, HSF1 may be useful as a diagnostic and prognostic biomarker for CRC. HSF1 was closely correlated with immune features. Genetic and epigenetic alterations contributed to HSF1 overexpression in CRC. More importantly, we demonstrated that HSF1 may be regulated at the level of mRNA translation by β-catenin-induced HuR activity.
DOI: 10.6084/m9.figshare.18126265.v1
title: Integrated bioinformatics and experiments reveal the roles and driving forces for HSF1 in colorectal cancer

description: Heat shock factor 1 (HSF1) has watershed significance in different tumors. However, the roles and driving forces for HSF1 in colorectal cancer (CRC) are poorly understood. Our study integrally analyzed the roles and driving forces for HSF1 in CRC by bioinformatics and experiments. The expression and prognostic characteristics of HSF1 were analyzed via UALCAN, GEPIA2, TISIDB, Prognoscan and HPA databases. Then, we analyzed the correlation between HSF1 expression and immune features via TIMER2 database. Subsequently, we explored the driving forces for HSF1 abnormal expression in CRC by bioinformatics and experiments. Our results showed that HSF1 was overexpressed and correlated with poor prognosis in CRC. And the expression of HSF1 was significantly correlated with multiple immune cell infiltration and was negatively correlated with immunomodulators such as programmed cell death 1 ligand 1(PD-L1). Along with many driver genes in particular <i>TP53</i>, super-enhancer, miRNA and DNA methylation were all responsible for HSF1 overexpression in CRC. Moreover, we demonstrated that β-catenin could promote the translation process of HSF1 mRNA by interacting with HuR, which could directly bind to the coding sequence (CDS) region of HSF1 mRNA. Collectively, HSF1 may be useful as a diagnostic and prognostic biomarker for CRC. HSF1 was closely correlated with immune features. Genetic and epigenetic alterations contributed to HSF1 overexpression in CRC. More importantly, we demonstrated that HSF1 may be regulated at the level of mRNA translation by β-catenin-induced HuR activity.
DOI: 10.6084/m9.figshare.18093833
title: New insights into aging-associated characteristics of female subcutaneous adipose tissue through integrative analysis of multi-omics data

description: Aging could be critical in limiting the application of subcutaneous adipose tissue (SAT) in tissue repair and reconstruction. However, no systematic study on the characteristics of SAT aging has been conducted. In this study, a scanning electronic microscope was used to detect the structural and compositional changes of SAT collected from nine females in three age groups. Multi-omics data of SAT from 37 females were obtained from Gene Expression Omnibus database, and 1860 genes, 56 miRNAs, and 332 methylated genes were identified as being differentially expressed during aging among non-obese females. Using Weighted Correlation Network Analysis (WGCNA), 1754 DEGs were defined as aging-associated genes for non-obese females, distributed among ten co-expression modules. Through Gene Ontology enrichment analysis and Gene Set enrichment analysis on those aging-associated DEGs, SAT aging was observed to be characterized by variations in immune and inflammatory states, mitochondria, lipid and carbohydrate metabolism, and regulation of vascular development. SUPV3L1, OGT, and ARPC1B were identified as conserved and core SAT-aging-related genes, as verified by RT-qPCR among 18 samples in different age groups. Multi-omics regulatory networks of core aging-associated biological processes of SAT were also constructed. Based on WGCNA, we performed differential co-expression analysis to unveil the differences in aging-related co-expression patterns between obese and non-obese females and determined that obesity could be an important accelerating factor in aging processes. Our work provides a landscape of SAT aging, which could be helpful for further research in fields such as repair and reconstruction as well as aging.
DOI: 10.6084/m9.figshare.18093833.v1
title: New insights into aging-associated characteristics of female subcutaneous adipose tissue through integrative analysis of multi-omics data

description: Aging could be critical in limiting the application of subcutaneous adipose tissue (SAT) in tissue repair and reconstruction. However, no systematic study on the characteristics of SAT aging has been conducted. In this study, a scanning electronic microscope was used to detect the structural and compositional changes of SAT collected from nine females in three age groups. Multi-omics data of SAT from 37 females were obtained from Gene Expression Omnibus database, and 1860 genes, 56 miRNAs, and 332 methylated genes were identified as being differentially expressed during aging among non-obese females. Using Weighted Correlation Network Analysis (WGCNA), 1754 DEGs were defined as aging-associated genes for non-obese females, distributed among ten co-expression modules. Through Gene Ontology enrichment analysis and Gene Set enrichment analysis on those aging-associated DEGs, SAT aging was observed to be characterized by variations in immune and inflammatory states, mitochondria, lipid and carbohydrate metabolism, and regulation of vascular development. SUPV3L1, OGT, and ARPC1B were identified as conserved and core SAT-aging-related genes, as verified by RT-qPCR among 18 samples in different age groups. Multi-omics regulatory networks of core aging-associated biological processes of SAT were also constructed. Based on WGCNA, we performed differential co-expression analysis to unveil the differences in aging-related co-expression patterns between obese and non-obese females and determined that obesity could be an important accelerating factor in aging processes. Our work provides a landscape of SAT aging, which could be helpful for further research in fields such as repair and reconstruction as well as aging.
DOI: 10.6084/m9.figshare.18462091
title: tRF-19-W4PU732S promotes breast cancer cell malignant activity by targeting inhibition of RPL27A (ribosomal protein-L27A)

description: Breast cancer (BC) is a serious threat to female health. tRNA-derived fragments (tRFs) are popular biomarkers for the diagnosis and treatment of cancer. The purpose of this study was to identify tRFs related to BC and to explore the function and regulatory mechanism of crucial tRFs in BC cells. Small RNA database was used to detect the tRF profiles from BC patients and controls. Differentially expressed tRFs were determined by quantitative reverse transcription PCR (RT-qPCR), and a crucial tRF was evaluated through silence and overexpression experiments, and the target gene was investigated by luciferase reporter gene assay, Western blot and rescue experiment. We screened tRF-19-W4PU732S, which was processed from the mature tRNA-Ser-AGA, and significantly highlyexpressed in BC tissues and cells. Inhibition of tRF-19-W4PU732S weakened MDA-MB-231 cell proliferation, migration and invasion, while enhanced apoptosis. On the contrary, overexpression of tRF-19-W4PU732S promoted MCF-7 cell proliferation, migration and invasion, whereasreduced apoptosis. Furthermore, tRF-19-W4PU732S induced BC cell epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSC) phenotypes, such as up-regulation of OCT-4A, SOX2 and Vimentin and down-regulation of E-cadherin. Ribosomal protein-L27A (RPL27A) was a downstream target of tRF-19-W4PU732S, which was lowly expressed in BC cells. The knockdown of RPL27A expression partially restored the promoting effects of tRF-19-W4PU732S on BC cell viability, invasion, migration, EMT and CSC phenotypes, and the suppression of apoptosis. In conclusion, our results manifested that tRF-19-W4PU732S promotes the malignant activity of BC cells by inhibiting RPL27A, which provides a new scientific basis for the treatment of BC. <b>Abbreviations</b> BC: breast cancer; tRNAs: transfer RNAs; tiRNAs: tRNA-derived stressinduced RNAs; tRFs: tRNA-derived fragments; CCK-8: Cell Counting Kit-8; PI: propidium iodide; EMT: epithelial-to-mesenchymal transition; CSC: cancer stem-like cells; RPL27A: ribosomal protein-L27A; RT-qPCR: quantitative reverse transcription PCR.
DOI: 10.6084/m9.figshare.18462091.v1
title: tRF-19-W4PU732S promotes breast cancer cell malignant activity by targeting inhibition of RPL27A (ribosomal protein-L27A)

description: Breast cancer (BC) is a serious threat to female health. tRNA-derived fragments (tRFs) are popular biomarkers for the diagnosis and treatment of cancer. The purpose of this study was to identify tRFs related to BC and to explore the function and regulatory mechanism of crucial tRFs in BC cells. Small RNA database was used to detect the tRF profiles from BC patients and controls. Differentially expressed tRFs were determined by quantitative reverse transcription PCR (RT-qPCR), and a crucial tRF was evaluated through silence and overexpression experiments, and the target gene was investigated by luciferase reporter gene assay, Western blot and rescue experiment. We screened tRF-19-W4PU732S, which was processed from the mature tRNA-Ser-AGA, and significantly highlyexpressed in BC tissues and cells. Inhibition of tRF-19-W4PU732S weakened MDA-MB-231 cell proliferation, migration and invasion, while enhanced apoptosis. On the contrary, overexpression of tRF-19-W4PU732S promoted MCF-7 cell proliferation, migration and invasion, whereasreduced apoptosis. Furthermore, tRF-19-W4PU732S induced BC cell epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSC) phenotypes, such as up-regulation of OCT-4A, SOX2 and Vimentin and down-regulation of E-cadherin. Ribosomal protein-L27A (RPL27A) was a downstream target of tRF-19-W4PU732S, which was lowly expressed in BC cells. The knockdown of RPL27A expression partially restored the promoting effects of tRF-19-W4PU732S on BC cell viability, invasion, migration, EMT and CSC phenotypes, and the suppression of apoptosis. In conclusion, our results manifested that tRF-19-W4PU732S promotes the malignant activity of BC cells by inhibiting RPL27A, which provides a new scientific basis for the treatment of BC. <b>Abbreviations</b> BC: breast cancer; tRNAs: transfer RNAs; tiRNAs: tRNA-derived stressinduced RNAs; tRFs: tRNA-derived fragments; CCK-8: Cell Counting Kit-8; PI: propidium iodide; EMT: epithelial-to-mesenchymal transition; CSC: cancer stem-like cells; RPL27A: ribosomal protein-L27A; RT-qPCR: quantitative reverse transcription PCR.
DOI: 10.6084/m9.figshare.18586137
title: Protective effect of liquiritin on coronary heart disease through regulating the proliferation of human vascular smooth muscle cells via upregulation of sirtuin1

description: This study aimed to explore whether liquiritin affects the development of coronary heart disease by regulating the proliferation and migration of human vascular smooth muscle cells (hVSMCs). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release detection were performed to measure the toxic effects of liquiritin on hVSMCs. An <i>in vitro</i> atherosclerosis model in hVSMCs was established using oxidized low-density lipoprotein (ox-LDL), and cell proliferation and apoptosis were detected using an MTT assay and flow cytometry analysis. Western blotting and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) were used to detect protein and mRNA expressions, respectively. Caspase3 activity and cell migration were measured using an activity detection kit and Transwell assay, respectively. The results indicated that liquiritin at doses &lt;160 μM had no significant effect on cell viability and LDH release in hVSMCs. Ox-LDL significantly induced cell proliferation and migration, and inhibited hVSMCs apoptosis. Liquiritin significantly inhibited cell proliferation and migration, and enhanced cell apoptosis in ox-LDL induced hVSMCs. Sirtuin1 (SIRT1) was lowly expressed in atherosclerotic plaque tissues in coronary heart disease patients and in ox-LDL-induced hVSMCs. Liquiritin improved SIRT1 expression in ox-LDL-induced hVSMCs, whereas the improvement was inhibited by Selisistat (EX 527, an effective SIRT1 inhibitor) treatment. EX 527 reversed the effects of liquiritin on cell proliferation, migration, and apoptosis in ox-LDL-induced hVSMCs In conclusion, liquiritin plays a protective role in coronary heart disease by regulating the proliferation and migration of hVSMCs by increasing SIRT1 expression.
DOI: 10.6084/m9.figshare.18586137.v1
title: Protective effect of liquiritin on coronary heart disease through regulating the proliferation of human vascular smooth muscle cells via upregulation of sirtuin1

description: This study aimed to explore whether liquiritin affects the development of coronary heart disease by regulating the proliferation and migration of human vascular smooth muscle cells (hVSMCs). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release detection were performed to measure the toxic effects of liquiritin on hVSMCs. An <i>in vitro</i> atherosclerosis model in hVSMCs was established using oxidized low-density lipoprotein (ox-LDL), and cell proliferation and apoptosis were detected using an MTT assay and flow cytometry analysis. Western blotting and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) were used to detect protein and mRNA expressions, respectively. Caspase3 activity and cell migration were measured using an activity detection kit and Transwell assay, respectively. The results indicated that liquiritin at doses &lt;160 μM had no significant effect on cell viability and LDH release in hVSMCs. Ox-LDL significantly induced cell proliferation and migration, and inhibited hVSMCs apoptosis. Liquiritin significantly inhibited cell proliferation and migration, and enhanced cell apoptosis in ox-LDL induced hVSMCs. Sirtuin1 (SIRT1) was lowly expressed in atherosclerotic plaque tissues in coronary heart disease patients and in ox-LDL-induced hVSMCs. Liquiritin improved SIRT1 expression in ox-LDL-induced hVSMCs, whereas the improvement was inhibited by Selisistat (EX 527, an effective SIRT1 inhibitor) treatment. EX 527 reversed the effects of liquiritin on cell proliferation, migration, and apoptosis in ox-LDL-induced hVSMCs In conclusion, liquiritin plays a protective role in coronary heart disease by regulating the proliferation and migration of hVSMCs by increasing SIRT1 expression.