cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19165809.v1
title: Long non-coding RNA TRPM2 antisense RNA as a potential therapeutic target promotes tumorigenesis and metastasis in esophageal cancer

description: Esophageal cancer (EC) is one type of aggressive gastrointestinal cancers. The treatment of EC is challenging. Effective therapeutic targets require development. Long non-coding RNA TRPM2 antisense RNA (LncRNA TRPM2-AS) is considering a novel biomarker and therapeutic target for various types of cancer. However, the role of lncRNA TRPM2-AS in EC remains unknown. This study aimed to illustrate effects of LncRNA TRPM2-AS on EC growth and metastasis and potential underlying molecular mechanisms. LncRNA TRPM2-AS expression was determined in both EC tissues and cell lines by quantitative real-time polymerase-chain reaction (qRT-PCR). Cell proliferation ability was evaluated by cell counting kit-8 and colony formation assays. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were determined using transwell. Epithelial–mesenchymal transition (EMT)-related markers expression were determined using qRT-PCR and Western blotting. Furthermore, potential lncRNA TRPM2-AS targeting miRNAs were predicted by public databases. The expression of five selected miRNAs were validated by qRT-PCR. We found that lncRNA TRPM2-AS expression was increased in EC tissues and cell lines compared with respective control. Silencing lncRNA TRPM2-AS suppressed EC cell proliferation, migration, and invasion while promoted cell apoptosis. Moreover, lncRNA TRPM2-AS knockdown reduced neural cadherin, vimentin, and matrix metallopeptidase 9 gene and protein expressions while increased epithelial cadherin expression. Furthermore, lncRNA TRPM2-AS knockdown promoted microRNA (miR)-1291, miR-6852-5p, and miR-138-5p expressions. Taken together, this study for the first time demonstrates that upregulation of lncRNA TRPM2-AS in EC promotes the growth and metastasis of EC likely through interacting with miR-1291, miR-6852-5p, and miR-138-5p.
DOI: 10.6084/m9.figshare.19131005
title: <i>Polygonum cuspidatum</i> inhibits the growth of osteosarcoma cells via impeding Akt/ERK/EGFR signaling pathways

description: Osteosarcoma (OS), the most prevalent bone malignancy, mainly affects children and adolescents. Despite recent advances in multimodal therapy, the overall survival rate for OS patients remains poor. Chinese herb medicine (CHM) is an alternative therapeutic option for multifaceted diseases such as malignant tumors. For centuries in China, <i>polygonum cuspidatum</i>, a classic CHM, has been used to treat several diseases, nevertheless, the mechanisms underlying its therapeutic effects have not been fully elucidated. Through network pharmacology and bioinformatic tools, we evaluated the pharmacological activity of <i>polygonum cuspidatum</i>. We found that it has a potential therapeutic effect on malignant tumors, which was subsequently verified by intragastric administration of <i>polygonum cuspidatum</i> to OS cell xenografted mice models. Next, to establish the action mechanism of <i>polygonum cuspidatum</i>, we built a disease/drug-target PPI network that was made up of 250 core treatment targets against OS using Cytoscape software. Enrichment evaluation for the above targets indicated that <i>polygonum cuspidatum</i> may exert its effects on the cell cycle and apoptosis of OS cells through inhibiting Akt/ERK/EGFR pathways. Finally, the above <i>in silico</i> results were experimentally validated via a series of molecular biological and cell functional analyses. Taken together, the findings show that <i>polygonum cuspidatum</i> has a significant potential for OS treatment, which provides a novel insight into the discovery of CHM-based drug against malignancies. CC: Closeness centrality; OS: Osteosarcoma; TCM: Traditional Chinese medicine; NSCLC: Non-small cell lung cancer; DC: Degree centrality; CHM: Chinese herb medicine; BC: Betweenness centrality
DOI: 10.6084/m9.figshare.19131005.v1
title: <i>Polygonum cuspidatum</i> inhibits the growth of osteosarcoma cells via impeding Akt/ERK/EGFR signaling pathways

description: Osteosarcoma (OS), the most prevalent bone malignancy, mainly affects children and adolescents. Despite recent advances in multimodal therapy, the overall survival rate for OS patients remains poor. Chinese herb medicine (CHM) is an alternative therapeutic option for multifaceted diseases such as malignant tumors. For centuries in China, <i>polygonum cuspidatum</i>, a classic CHM, has been used to treat several diseases, nevertheless, the mechanisms underlying its therapeutic effects have not been fully elucidated. Through network pharmacology and bioinformatic tools, we evaluated the pharmacological activity of <i>polygonum cuspidatum</i>. We found that it has a potential therapeutic effect on malignant tumors, which was subsequently verified by intragastric administration of <i>polygonum cuspidatum</i> to OS cell xenografted mice models. Next, to establish the action mechanism of <i>polygonum cuspidatum</i>, we built a disease/drug-target PPI network that was made up of 250 core treatment targets against OS using Cytoscape software. Enrichment evaluation for the above targets indicated that <i>polygonum cuspidatum</i> may exert its effects on the cell cycle and apoptosis of OS cells through inhibiting Akt/ERK/EGFR pathways. Finally, the above <i>in silico</i> results were experimentally validated via a series of molecular biological and cell functional analyses. Taken together, the findings show that <i>polygonum cuspidatum</i> has a significant potential for OS treatment, which provides a novel insight into the discovery of CHM-based drug against malignancies. CC: Closeness centrality; OS: Osteosarcoma; TCM: Traditional Chinese medicine; NSCLC: Non-small cell lung cancer; DC: Degree centrality; CHM: Chinese herb medicine; BC: Betweenness centrality
DOI: 10.6084/m9.figshare.18514995
title: The hsa_circRNA_102049 mediates the sorafenib sensitivity of hepatocellular carcinoma cells by regulating <i>Reelin</i> gene expression

description: A growing body of research has illuminated that non-coding RNAs (ncRNAs) plays an important role in the development of drug resistance in hepatocellular carcinoma (HCC) cells. The expression profiles of differential expressed genes (DEGs) and ncRNAs related to the sorafenib resistance in HCC cells were analyzed according to the Gene Expression Omnibus (GEO) dataSets and The Cancer Genome Atlas (TCGA) datasets. Bioinformatics technology was used to construct the interaction network of DEGs and ncRNAs. Cell transfection, dual-luciferase reporter assay, Western blot, cell counting kit-8 (CCK-8), flow cytometry and quantitative real-time polymerase chain reaction(qRT-PCR) were used to study the mechanism of sorafenib resistance in HepG2 cells and Huh-7 cells. The expression of reelin (RELN) and secretagogin (SCGN) were the only down-regulated in sorafenib-resistant HCC cells. The results showed that <i>RELN</i> gene demethylation reversed the cytotoxic of sorafenib on HepG2 cells and Huh-7 cells. Hsa_circRNA_102049 over-expression promoted the sensitivity of HepG2 cells and Huh-7 cells to sorafenib, hsa_circRNA_102049 up-regulated the expression of <i>RELN</i> gene by sponging hsa-miR-214-3p. The resistance to sorafenib in RELN knockout HepG2 cells and Huh-7 cells could be reverted by has-circRNA_102049. These findings support targeting of hsa_circRNA_102049 and RELN in sorafenib-treated HCC cells as a novel intervention, which is expected to overcome sorafenib resistance of HCC cells.
DOI: 10.6084/m9.figshare.18514995.v1
title: The hsa_circRNA_102049 mediates the sorafenib sensitivity of hepatocellular carcinoma cells by regulating <i>Reelin</i> gene expression

description: A growing body of research has illuminated that non-coding RNAs (ncRNAs) plays an important role in the development of drug resistance in hepatocellular carcinoma (HCC) cells. The expression profiles of differential expressed genes (DEGs) and ncRNAs related to the sorafenib resistance in HCC cells were analyzed according to the Gene Expression Omnibus (GEO) dataSets and The Cancer Genome Atlas (TCGA) datasets. Bioinformatics technology was used to construct the interaction network of DEGs and ncRNAs. Cell transfection, dual-luciferase reporter assay, Western blot, cell counting kit-8 (CCK-8), flow cytometry and quantitative real-time polymerase chain reaction(qRT-PCR) were used to study the mechanism of sorafenib resistance in HepG2 cells and Huh-7 cells. The expression of reelin (RELN) and secretagogin (SCGN) were the only down-regulated in sorafenib-resistant HCC cells. The results showed that <i>RELN</i> gene demethylation reversed the cytotoxic of sorafenib on HepG2 cells and Huh-7 cells. Hsa_circRNA_102049 over-expression promoted the sensitivity of HepG2 cells and Huh-7 cells to sorafenib, hsa_circRNA_102049 up-regulated the expression of <i>RELN</i> gene by sponging hsa-miR-214-3p. The resistance to sorafenib in RELN knockout HepG2 cells and Huh-7 cells could be reverted by has-circRNA_102049. These findings support targeting of hsa_circRNA_102049 and RELN in sorafenib-treated HCC cells as a novel intervention, which is expected to overcome sorafenib resistance of HCC cells.
DOI: 10.6084/m9.figshare.19145336
title: LncRNA miR-17-92a-1 cluster host gene (MIR17HG) promotes neuronal damage and microglial activation by targeting the microRNA-153-3p/alpha-synuclein axis in Parkinson’s disease

description: Long noncoding RNAs (lncRNAs) have been regarded as modulators of neurodegenerative diseases. Here, we addressed the role of lncRNA miR-17-92a-1 cluster host gene (MIR17HG) in Parkinson’s disease (PD). C57BL/6 mice and SH-SY5Y cells were intervened with 6-hydroxydopamine (6-OHDA) to set up PD models <i>in vivo</i> and <i>in vitro</i>. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was implemented to compare the expression of MIR17HG and miR-153-3p. Cell viability and apoptosis were estimated by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and Western blot (WB). The expression of alpha-synuclein (α-syn, SNCA) in BV2 was validated by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were evaluated using commercially available kits. Bioinformatics analysis, the dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and qRT-PCR were conducted to demonstrate the interactions between miR-153-3p, MIR17HG, and alpha-synuclein (SNCA). MIR17HG was up-regulated while miR-153-3p was down-regulated in PD patients, mouse models and cells. Inhibiting MIR17HG attenuated neuronal apoptosis, microglial activation and SNCA expression in PD mice. Conditioned medium from 6-OHDA-treated SH-SY5Y cells intensified microglial inflammation, while inhibition of MIR17HG or overexpression of miR-153-3p restrained the inflammatory responses. MIR17HG’s function was enforced by sponging miR-153-3p and releasing the attenuation of the putative targets of miR-153-3p and SNCA. Overall, MIR17HG, by targeting miR-153-3p and up-regulating SNCA, stimulates neuronal apoptosis and microglial inflammation in PD.
DOI: 10.6084/m9.figshare.19145336.v1
title: LncRNA miR-17-92a-1 cluster host gene (MIR17HG) promotes neuronal damage and microglial activation by targeting the microRNA-153-3p/alpha-synuclein axis in Parkinson’s disease

description: Long noncoding RNAs (lncRNAs) have been regarded as modulators of neurodegenerative diseases. Here, we addressed the role of lncRNA miR-17-92a-1 cluster host gene (MIR17HG) in Parkinson’s disease (PD). C57BL/6 mice and SH-SY5Y cells were intervened with 6-hydroxydopamine (6-OHDA) to set up PD models <i>in vivo</i> and <i>in vitro</i>. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was implemented to compare the expression of MIR17HG and miR-153-3p. Cell viability and apoptosis were estimated by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and Western blot (WB). The expression of alpha-synuclein (α-syn, SNCA) in BV2 was validated by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were evaluated using commercially available kits. Bioinformatics analysis, the dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and qRT-PCR were conducted to demonstrate the interactions between miR-153-3p, MIR17HG, and alpha-synuclein (SNCA). MIR17HG was up-regulated while miR-153-3p was down-regulated in PD patients, mouse models and cells. Inhibiting MIR17HG attenuated neuronal apoptosis, microglial activation and SNCA expression in PD mice. Conditioned medium from 6-OHDA-treated SH-SY5Y cells intensified microglial inflammation, while inhibition of MIR17HG or overexpression of miR-153-3p restrained the inflammatory responses. MIR17HG’s function was enforced by sponging miR-153-3p and releasing the attenuation of the putative targets of miR-153-3p and SNCA. Overall, MIR17HG, by targeting miR-153-3p and up-regulating SNCA, stimulates neuronal apoptosis and microglial inflammation in PD.
DOI: 10.6084/m9.figshare.19168115
title: Uric acid, as a double-edged sword, affects the activity of epidermal growth factor (EGF) on human umbilical vein endothelial cells by regulating aging process

description: Uric acid (UA) is the main metabolite of the human body. Although UA is only a product of metabolism, it is important biological regulator. Epidermal growth factor (EGF) has important biological functions. However, so far, the effect of UA on EGF’s activity has not been revealed. For this, in the current study, we systematically studied the effect of OA on the biological activity of EGF. Human Umbilical Vein Endothelial Cells (HUVECs) were used as an <i>in vitro</i> model, and Western-blot, RT-PCR, laser scanning confocal microscopy (CLSM) and co-localization analyses were carried out. The results showed that high concentration of UA (10 mg/dl) severely affected the biological activity of EGF. High concentration of UA suppressed the activity of EGF, and inhibited the biological effect of EGF on the HUVECs. However, it is interesting that EGF-mediated intracellular signaling was significantly down-regulated in the H<sub>2</sub>O<sub>2</sub>-induced senescent HUVEC, and physiological concentration of UA could at least partially restore the EGF-mediated signaling. Further work showed that physiological concentration of UA (5 mg/dl) shows the anti-aging effect. Taken together, current research indicates that UA may be a ‘double-edged sword’, physiological concentration of UA may be beneficial, but high concentrations of uric acid (UA) are harmful.
DOI: 10.6084/m9.figshare.19168115.v1
title: Uric acid, as a double-edged sword, affects the activity of epidermal growth factor (EGF) on human umbilical vein endothelial cells by regulating aging process

description: Uric acid (UA) is the main metabolite of the human body. Although UA is only a product of metabolism, it is important biological regulator. Epidermal growth factor (EGF) has important biological functions. However, so far, the effect of UA on EGF’s activity has not been revealed. For this, in the current study, we systematically studied the effect of OA on the biological activity of EGF. Human Umbilical Vein Endothelial Cells (HUVECs) were used as an <i>in vitro</i> model, and Western-blot, RT-PCR, laser scanning confocal microscopy (CLSM) and co-localization analyses were carried out. The results showed that high concentration of UA (10 mg/dl) severely affected the biological activity of EGF. High concentration of UA suppressed the activity of EGF, and inhibited the biological effect of EGF on the HUVECs. However, it is interesting that EGF-mediated intracellular signaling was significantly down-regulated in the H<sub>2</sub>O<sub>2</sub>-induced senescent HUVEC, and physiological concentration of UA could at least partially restore the EGF-mediated signaling. Further work showed that physiological concentration of UA (5 mg/dl) shows the anti-aging effect. Taken together, current research indicates that UA may be a ‘double-edged sword’, physiological concentration of UA may be beneficial, but high concentrations of uric acid (UA) are harmful.
DOI: 10.6084/m9.figshare.20017686
title: Long non-coding RNA LINRIS is upregulated in non-small cell lung cancer and its silencing inhibits cell proliferation by suppressing microRNA-10a maturation

description: Long noncoding RNA LINRIS (LINC00920) is known to participate in colorectal cancer. This study aimed to explore the role of LINRIS in non-small cell lung cancer (NSCLC). NSCLC and adjacent non-tumor tissues were collected from 62 NSCLC patients. LINRIS expression was detected using real-time quantitative PCR (RT-qPCRs). The 62 NSCLC patients were monitored every month for 5 years to evaluate the role of LINRIS in predicting the prognosis of NSCLC. The effects of LINRIS silencing on microRNA-10a (miR-10a) precursor and mature miR-10a levels were assessed by RT-qPCR. Cell proliferation was measured using Cell Counting Kit-8 (CCK-8) assays. LINRIS expression was upregulated in NSCLC tissues. High LINRIS levels predicted poor survival of NSCLC patients. LINRIS were positively correlated with mature (miR-10a) levels but not miR-10a precursor. In NSCLC cells, LINRIS silencing showed no role in miR-10a precursor accumulation but downregulated mature miR10a level. Moreover, LINRIS silencing inhibited cell proliferation, while miR-10a overexpression increased cell proliferation and inhibited the role of LINRIS silencing. Overall, LINRIS silencing may inhibit NSCLC cell proliferation by suppressing miR-10a maturation. <b>Abbreviations:</b> Non-small cell lung cancer (NSCLC); Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR); LncRNA long intergenic noncoding RNA for IGF2BP2 stability (LINRIS).
DOI: 10.6084/m9.figshare.20017686.v1
title: Long non-coding RNA LINRIS is upregulated in non-small cell lung cancer and its silencing inhibits cell proliferation by suppressing microRNA-10a maturation

description: Long noncoding RNA LINRIS (LINC00920) is known to participate in colorectal cancer. This study aimed to explore the role of LINRIS in non-small cell lung cancer (NSCLC). NSCLC and adjacent non-tumor tissues were collected from 62 NSCLC patients. LINRIS expression was detected using real-time quantitative PCR (RT-qPCRs). The 62 NSCLC patients were monitored every month for 5 years to evaluate the role of LINRIS in predicting the prognosis of NSCLC. The effects of LINRIS silencing on microRNA-10a (miR-10a) precursor and mature miR-10a levels were assessed by RT-qPCR. Cell proliferation was measured using Cell Counting Kit-8 (CCK-8) assays. LINRIS expression was upregulated in NSCLC tissues. High LINRIS levels predicted poor survival of NSCLC patients. LINRIS were positively correlated with mature (miR-10a) levels but not miR-10a precursor. In NSCLC cells, LINRIS silencing showed no role in miR-10a precursor accumulation but downregulated mature miR10a level. Moreover, LINRIS silencing inhibited cell proliferation, while miR-10a overexpression increased cell proliferation and inhibited the role of LINRIS silencing. Overall, LINRIS silencing may inhibit NSCLC cell proliferation by suppressing miR-10a maturation. <b>Abbreviations:</b> Non-small cell lung cancer (NSCLC); Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR); LncRNA long intergenic noncoding RNA for IGF2BP2 stability (LINRIS).
DOI: 10.6084/m9.figshare.18462085
title: Prospero homeobox 1 promotes proliferation, migration, and invasion of osteosarcoma cells and its clinical significance

description: Osteosarcoma (OS) is the most common primary malignant bone tumor. Prospero homeobox 1 (PROX1) is a key transcription factor involved in some cancers, but the role of PROX1 in OS is unclear. This study aimed to explore the clinical and biology significance of PROX1 in OS. Fifty-four OS tissues and matched nontumor tissues were collected to explore the relationship between <i>PROX1</i> expression and clinical characteristics and prognosis. qRT-PCR and immunohistochemistry were used to investigate the expression patterns of PROX1 in OS tissues and cells. CCK-8, wound healing, and transwell assays were used to detect the effects of PROX1 on the proliferation, migration, and invasion of OS cells. Transcriptome sequencing, bioinformatics analysis and qRT-PCR were used to explore the regulatory network of PROX1. PROX1 was significantly higher in OS tissues and cells compared to normal tissues and cell lines. In OS patients, high expression of PROX1 was associated with Enneking stage (P &lt; 0.001) and M classification (P &lt; 0.001). High PROX1 expression predicted a poorer overall survival (P = 0.0047). Compared with untreated cells, OS cells overexpressing <i>PROX1</i> showed higher proliferation, migration, and invasion abilities, while knockdown of <i>PROX1</i> suppressed these abilities. The results of Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the down regulated genes were mainly enriched in TNF signaling pathway, MAPK signaling pathway, and neuroactive ligand-receptor interaction. High <i>PROX1</i> expression was significantly associated with poor overall survival in OS patients. PROX1 may be a promising prognostic marker and therapeutic target for OS patients.
DOI: 10.6084/m9.figshare.18462085.v1
title: Prospero homeobox 1 promotes proliferation, migration, and invasion of osteosarcoma cells and its clinical significance

description: Osteosarcoma (OS) is the most common primary malignant bone tumor. Prospero homeobox 1 (PROX1) is a key transcription factor involved in some cancers, but the role of PROX1 in OS is unclear. This study aimed to explore the clinical and biology significance of PROX1 in OS. Fifty-four OS tissues and matched nontumor tissues were collected to explore the relationship between <i>PROX1</i> expression and clinical characteristics and prognosis. qRT-PCR and immunohistochemistry were used to investigate the expression patterns of PROX1 in OS tissues and cells. CCK-8, wound healing, and transwell assays were used to detect the effects of PROX1 on the proliferation, migration, and invasion of OS cells. Transcriptome sequencing, bioinformatics analysis and qRT-PCR were used to explore the regulatory network of PROX1. PROX1 was significantly higher in OS tissues and cells compared to normal tissues and cell lines. In OS patients, high expression of PROX1 was associated with Enneking stage (P &lt; 0.001) and M classification (P &lt; 0.001). High PROX1 expression predicted a poorer overall survival (P = 0.0047). Compared with untreated cells, OS cells overexpressing <i>PROX1</i> showed higher proliferation, migration, and invasion abilities, while knockdown of <i>PROX1</i> suppressed these abilities. The results of Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the down regulated genes were mainly enriched in TNF signaling pathway, MAPK signaling pathway, and neuroactive ligand-receptor interaction. High <i>PROX1</i> expression was significantly associated with poor overall survival in OS patients. PROX1 may be a promising prognostic marker and therapeutic target for OS patients.