cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.14705040
title: Long non-coding RNA histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) inhibits HDAC4 expression in human ARPE-19 cells with hypoxic stress

description: Age-related macular degeneration (AMD) is resulted from choroidal neovascularization (CNV)-mediated cicatrization and vision loss. The sustained retinal hypoxia in retinal pigment epithelium (RPE) cells was reported to contribute to CNV. However, the underlying genetic regulatory network of hypoxia response in RPE is not fully understood. In this study, human ARPE-19 RPE cells were cultured under the anoxia for 24 h and later re-oxygenated in normoxia. Then the transcriptome was investigated via high throughput sequencing. We observed that long non-coding RNA (lncRNA) histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) was increased in hypoxic condition compared to normal control and decreased after re-oxygenation addition, while the change of HDAC4 expression was reduced in hypoxic condition compared to normal control and up-regulated after re-oxygenation addition in ARPE-19 cells. Furthermore, HDAC4-AS1 knockdown could suppress the transcription activity of HDAC4 only in hypoxia condition, and fluorescence in situ hybridization and pull down assay indicated that transcripts of HDAC4-AS1 could substantially bind to the promoter of HDAC4 and facilitate the recruitment of HIF-1α. Finally, we also determined the specific regions of HDAC4-AS1 that contribute to the interaction with HIF-1α and the promoter of HDAC4. Taken together, these outcomes declared that HDAC4-AS1 could inhibit HDAC4 expression through regulating HIF-1α in human ARPE-19 cells with hypoxic stress.
DOI: 10.6084/m9.figshare.14705040.v1
title: Long non-coding RNA histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) inhibits HDAC4 expression in human ARPE-19 cells with hypoxic stress

description: Age-related macular degeneration (AMD) is resulted from choroidal neovascularization (CNV)-mediated cicatrization and vision loss. The sustained retinal hypoxia in retinal pigment epithelium (RPE) cells was reported to contribute to CNV. However, the underlying genetic regulatory network of hypoxia response in RPE is not fully understood. In this study, human ARPE-19 RPE cells were cultured under the anoxia for 24 h and later re-oxygenated in normoxia. Then the transcriptome was investigated via high throughput sequencing. We observed that long non-coding RNA (lncRNA) histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) was increased in hypoxic condition compared to normal control and decreased after re-oxygenation addition, while the change of HDAC4 expression was reduced in hypoxic condition compared to normal control and up-regulated after re-oxygenation addition in ARPE-19 cells. Furthermore, HDAC4-AS1 knockdown could suppress the transcription activity of HDAC4 only in hypoxia condition, and fluorescence in situ hybridization and pull down assay indicated that transcripts of HDAC4-AS1 could substantially bind to the promoter of HDAC4 and facilitate the recruitment of HIF-1α. Finally, we also determined the specific regions of HDAC4-AS1 that contribute to the interaction with HIF-1α and the promoter of HDAC4. Taken together, these outcomes declared that HDAC4-AS1 could inhibit HDAC4 expression through regulating HIF-1α in human ARPE-19 cells with hypoxic stress.
DOI: 10.6084/m9.figshare.21070678.v2
title: Additional file and SYSTEM DATA.zip

description: Additional file and System data
DOI: 10.6084/m9.figshare.21070678.v1
title: Additional file and SYSTEM DATA.zip

description: Additional file and System data
DOI: 10.6084/m9.figshare.16570728.v2
title: Integrated analysis of hypoxia-associated lncRNA signature to predict prognosis and immune microenvironment of lung adenocarcinoma patients

description: Lung adenocarcinoma (LUAD) represents the main lung cancer (LC) subtype that possesses a disappointing clinical outcome over the decades. Tumor hypoxia is closely bound up with dismal survival for malignant tumor cases. We identified hypoxia-associated long non-coding RNA (lncRNA) signature to be an explicit indicator for predicting prognosis. The present work acquired RNA-seq and associated clinical data from The Cancer Genome Atlas (TCGA) database. Consensus cluster analysis characterized the hypoxia status of LUAD patients. Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) method determined significantly prognosis-related lncRNAs which were used to create a prognostic model. Diverse statistical approaches like the Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and nomogram were adopted to verify the accuracy of the risk score. The potential immune environment landscape was unearthed by the CIBERSORT algorithm. Three hypoxia-related clusters were determined and 221 differentially expressed hypoxia-related lncRNAs were screened out. We developed a new predictive model based on seven lncRNAs (LINC00941, AC022784.1, AC079949.2, LINC00707, AL161431.1, AC010980.2 and AC090001.1). Kaplan-Meier curves and ROC plots uncovered the reliable predictive power of the risk score model. In addition, the immunosuppressive landscape was presented in the high-risk group by immune cell infiltration analysis. The seven hypoxia lncRNAs survival signature in our article are robust, accurate tools for predicting overall survival in LUAD patients.
DOI: 10.6084/m9.figshare.16570728
title: Integrated analysis of hypoxia-associated lncRNA signature to predict prognosis and immune microenvironment of lung adenocarcinoma patients

description: Lung adenocarcinoma (LUAD) represents the main lung cancer (LC) subtype that possesses a disappointing clinical outcome over the decades. Tumor hypoxia is closely bound up with dismal survival for malignant tumor cases. We identified hypoxia-associated long non-coding RNA (lncRNA) signature to be an explicit indicator for predicting prognosis. The present work acquired RNA-seq and associated clinical data from The Cancer Genome Atlas (TCGA) database. Consensus cluster analysis characterized the hypoxia status of LUAD patients. Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) method determined significantly prognosis-related lncRNAs which were used to create a prognostic model. Diverse statistical approaches like the Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and nomogram were adopted to verify the accuracy of the risk score. The potential immune environment landscape was unearthed by the CIBERSORT algorithm. Three hypoxia-related clusters were determined and 221 differentially expressed hypoxia-related lncRNAs were screened out. We developed a new predictive model based on seven lncRNAs (LINC00941, AC022784.1, AC079949.2, LINC00707, AL161431.1, AC010980.2 and AC090001.1). Kaplan-Meier curves and ROC plots uncovered the reliable predictive power of the risk score model. In addition, the immunosuppressive landscape was presented in the high-risk group by immune cell infiltration analysis. The seven hypoxia lncRNAs survival signature in our article are robust, accurate tools for predicting overall survival in LUAD patients.
DOI: 10.6084/m9.figshare.16570728.v1
title: Integrated analysis of hypoxia-associated lncRNA signature to predict prognosis and immune microenvironment of lung adenocarcinoma patients

description: Lung adenocarcinoma (LUAD) represents the main lung cancer (LC) subtype that possesses a disappointing clinical outcome over the decades. Tumor hypoxia is closely bound up with dismal survival for malignant tumor cases. We identified hypoxia-associated long non-coding RNA (lncRNA) signature to be an explicit indicator for predicting prognosis. The present work acquired RNA-seq and associated clinical data from The Cancer Genome Atlas (TCGA) database. Consensus cluster analysis characterized the hypoxia status of LUAD patients. Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) method determined significantly prognosis-related lncRNAs which were used to create a prognostic model. Diverse statistical approaches like the Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and nomogram were adopted to verify the accuracy of the risk score. The potential immune environment landscape was unearthed by the CIBERSORT algorithm. Three hypoxia-related clusters were determined and 221 differentially expressed hypoxia-related lncRNAs were screened out. We developed a new predictive model based on seven lncRNAs (LINC00941, AC022784.1, AC079949.2, LINC00707, AL161431.1, AC010980.2 and AC090001.1). Kaplan-Meier curves and ROC plots uncovered the reliable predictive power of the risk score model. In addition, the immunosuppressive landscape was presented in the high-risk group by immune cell infiltration analysis. The seven hypoxia lncRNAs survival signature in our article are robust, accurate tools for predicting overall survival in LUAD patients.
DOI: 10.6084/m9.figshare.16699358
title: Alteration of long non-coding RNAs and mRNAs expression profiles by compound heterozygous ASXL3 mutations in the mouse brain

description: Compound mutations in the additional sex combs-like 3 (ASXL3) gene greatly impact the expression of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in mouse myocardial tissues. Little is known about ASXL3 mutation effects on lncRNAs and mRNAs expression in the cerebrum and cerebellum. This study aims to clarify this point using quantitative real-time polymerase chain reaction and Western blotting. Transcriptome analysis based on RNA-seq followed by bioinformatics analysis were used to compare lncRNA and mRNA expression profiles. Cell proliferation, cell cycle progression, and apoptosis were evaluated after silencing of ASXL3 expression using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2 H-tetrazolium method and flow cytometry. Results showed that ASXL3 gene expression was decreased in the cerebrum and cerebellum of mice with ASXL3 P723R*P1817A mutations. We identified 319 lncRNAs and 252 mRNAs differentially expressed in the cerebrum of ASXL3 P723R*P1817A mutant mice. In the cerebellum of ASXL3 P723R*P1817A mutant mice, 5330 lncRNAs and 2204 mRNAs were differentially expressed. Differentially expressed lncRNAs and mRNAs were widely distributed across the mouse genome and were associated with various biological processes and pathways. ASXL3 silencing by siRNA transfection affected the proliferation, cell cycle progression, and apoptosis of neural cells. Therefore, the ASXL3 P723R*P1817A mutations greatly modify the lncRNA and mRNA expression profiles in the mouse cerebrum and cerebellum.
DOI: 10.6084/m9.figshare.16699358.v2
title: Alteration of long non-coding RNAs and mRNAs expression profiles by compound heterozygous ASXL3 mutations in the mouse brain

description: Compound mutations in the additional sex combs-like 3 (ASXL3) gene greatly impact the expression of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in mouse myocardial tissues. Little is known about ASXL3 mutation effects on lncRNAs and mRNAs expression in the cerebrum and cerebellum. This study aims to clarify this point using quantitative real-time polymerase chain reaction and Western blotting. Transcriptome analysis based on RNA-seq followed by bioinformatics analysis were used to compare lncRNA and mRNA expression profiles. Cell proliferation, cell cycle progression, and apoptosis were evaluated after silencing of ASXL3 expression using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2 H-tetrazolium method and flow cytometry. Results showed that ASXL3 gene expression was decreased in the cerebrum and cerebellum of mice with ASXL3 P723R*P1817A mutations. We identified 319 lncRNAs and 252 mRNAs differentially expressed in the cerebrum of ASXL3 P723R*P1817A mutant mice. In the cerebellum of ASXL3 P723R*P1817A mutant mice, 5330 lncRNAs and 2204 mRNAs were differentially expressed. Differentially expressed lncRNAs and mRNAs were widely distributed across the mouse genome and were associated with various biological processes and pathways. ASXL3 silencing by siRNA transfection affected the proliferation, cell cycle progression, and apoptosis of neural cells. Therefore, the ASXL3 P723R*P1817A mutations greatly modify the lncRNA and mRNA expression profiles in the mouse cerebrum and cerebellum.
DOI: 10.6084/m9.figshare.14912715
title: Identification and validation of a five-lncRNA signature for predicting survival with targeted drug candidates in ovarian cancer

description: The dysregulation of long non-coding RNAs (lncRNAs) plays a crucial role in ovarian cancer (OC). In this study, we screened out five differentially expressed lncRNAs <i>(AC092718.4, AC138035.1, BMPR1B-DT, RNF157-AS1,</i> and <i>TPT1-AS1)</i> between OC and normal ovarian based on TCGA and GTEx RNA-seq databases by using Kaplan–Meier analysis and univariate Cox, LASSO, and multivariate Cox regression. Then, a risk signature was constructed, with 1, 3, 5-year survival prediction accuracy confirmed by ROC curves, and an online survival calculator for easier clinical use. With lncRNA-microRNA-mRNA regulatory networks established, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, suggesting the involvement of a variety of cancer-related functions and pathways. Finally, five candidate small-molecule drugs (thioridazine, trifluoperazine, loperamide, LY294002, and puromycin) were predicted by Connectivity Map. In conclusion, we identified a 5-lncRNA signature of prognostic value with its ceRNA networks, and five candidate drugs against OC.
DOI: 10.6084/m9.figshare.14912715.v1
title: Identification and validation of a five-lncRNA signature for predicting survival with targeted drug candidates in ovarian cancer

description: The dysregulation of long non-coding RNAs (lncRNAs) plays a crucial role in ovarian cancer (OC). In this study, we screened out five differentially expressed lncRNAs <i>(AC092718.4, AC138035.1, BMPR1B-DT, RNF157-AS1,</i> and <i>TPT1-AS1)</i> between OC and normal ovarian based on TCGA and GTEx RNA-seq databases by using Kaplan–Meier analysis and univariate Cox, LASSO, and multivariate Cox regression. Then, a risk signature was constructed, with 1, 3, 5-year survival prediction accuracy confirmed by ROC curves, and an online survival calculator for easier clinical use. With lncRNA-microRNA-mRNA regulatory networks established, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, suggesting the involvement of a variety of cancer-related functions and pathways. Finally, five candidate small-molecule drugs (thioridazine, trifluoperazine, loperamide, LY294002, and puromycin) were predicted by Connectivity Map. In conclusion, we identified a 5-lncRNA signature of prognostic value with its ceRNA networks, and five candidate drugs against OC.
DOI: 10.6084/m9.figshare.16699358.v1
title: Alteration of long non-coding RNAs and mRNAs expression profiles by compound heterozygous ASXL3 mutations in the mouse brain

description: Compound mutations in the additional sex combs-like 3 (ASXL3) gene greatly impact the expression of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in mouse myocardial tissues. Little is known about ASXL3 mutation effects on lncRNAs and mRNAs expression in the cerebrum and cerebellum. This study aims to clarify this point using quantitative real-time polymerase chain reaction and Western blotting. Transcriptome analysis based on RNA-seq followed by bioinformatics analysis were used to compare lncRNA and mRNA expression profiles. Cell proliferation, cell cycle progression, and apoptosis were evaluated after silencing of ASXL3 expression using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2 H-tetrazolium method and flow cytometry. Results showed that ASXL3 gene expression was decreased in the cerebrum and cerebellum of mice with ASXL3 P723R*P1817A mutations. We identified 319 lncRNAs and 252 mRNAs differentially expressed in the cerebrum of ASXL3 P723R*P1817A mutant mice. In the cerebellum of ASXL3 P723R*P1817A mutant mice, 5330 lncRNAs and 2204 mRNAs were differentially expressed. Differentially expressed lncRNAs and mRNAs were widely distributed across the mouse genome and were associated with various biological processes and pathways. ASXL3 silencing by siRNA transfection affected the proliferation, cell cycle progression, and apoptosis of neural cells. Therefore, the ASXL3 P723R*P1817A mutations greatly modify the lncRNA and mRNA expression profiles in the mouse cerebrum and cerebellum.
DOI: 10.6084/m9.figshare.14761506
title: Targeting the miR-6734-3p/ZEB2 axis hampers development of non-small cell lung cancer (NSCLC) and increases susceptibility of cancer cells to cisplatin treatment

description: The unclear pathogenesis mechanisms and resistance of cancer cells to chemical drugs serious limits the development of effective treatment strategies for non-small cell lung cancer (NSCLC). In this study, we managed to investigate this issue, and identify potential cancer associated biomarkers for NSCLC diagnosis, prognosis and treatment. This study found that miR-6734-3p was downregulated in both NSCLC clinical specimens (tissues and serum) and cells, compared to the normal tissues and cells. Next, upregulation of miR-6734-3p inhibited cancer formation and progression in NSCLC cells <i>in vitro</i> and <i>in vivo</i>. Conversely, miR-6734-3p ablation had opposite effects and facilitated NSCLC development. In addition, miR-6734-3p bound to the 3ʹ untranslated region (3ʹUTR) of zinc finger E-box binding homeobox 2 (ZEB2) mRNA to suppress its expressions in NSCLC cells. Interestingly, the inhibiting effects of miR-6734-3p overexpression on NSCLC progression were abrogated by upregulating ZEB2. Furthermore, both upregulated miR-6734-3p and silencing of ZEB2 increased cisplatin-sensitivity in cisplatin-resistant NSCLC (CR-NSCLC) cells. Taken together, miR-6734-3p played an anti-tumor role to hinder cancer development and enhanced the cytotoxic effects of cisplatin treatment on NSCLC cells by downregulating ZEB2.
DOI: 10.6084/m9.figshare.14761506.v1
title: Targeting the miR-6734-3p/ZEB2 axis hampers development of non-small cell lung cancer (NSCLC) and increases susceptibility of cancer cells to cisplatin treatment

description: The unclear pathogenesis mechanisms and resistance of cancer cells to chemical drugs serious limits the development of effective treatment strategies for non-small cell lung cancer (NSCLC). In this study, we managed to investigate this issue, and identify potential cancer associated biomarkers for NSCLC diagnosis, prognosis and treatment. This study found that miR-6734-3p was downregulated in both NSCLC clinical specimens (tissues and serum) and cells, compared to the normal tissues and cells. Next, upregulation of miR-6734-3p inhibited cancer formation and progression in NSCLC cells <i>in vitro</i> and <i>in vivo</i>. Conversely, miR-6734-3p ablation had opposite effects and facilitated NSCLC development. In addition, miR-6734-3p bound to the 3ʹ untranslated region (3ʹUTR) of zinc finger E-box binding homeobox 2 (ZEB2) mRNA to suppress its expressions in NSCLC cells. Interestingly, the inhibiting effects of miR-6734-3p overexpression on NSCLC progression were abrogated by upregulating ZEB2. Furthermore, both upregulated miR-6734-3p and silencing of ZEB2 increased cisplatin-sensitivity in cisplatin-resistant NSCLC (CR-NSCLC) cells. Taken together, miR-6734-3p played an anti-tumor role to hinder cancer development and enhanced the cytotoxic effects of cisplatin treatment on NSCLC cells by downregulating ZEB2.
DOI: 10.6084/m9.figshare.15049140.v2
title: Estimation of polymorphisms in the drug-metabolizing enzyme, cytochrome <i>P450 2C19</i> gene in six major ethnicities of Pakistan

description: Interindividual differences in cytochrome P450 (<i>CYP)</i> 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for <i>CYP2C19*2</i> and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for <i>CYP2C19*2</i> and 8.14% for CYP2C19*3. For <i>CYP2C19*2</i>, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for <i>CYP2C19*3</i>, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19.
DOI: 10.6084/m9.figshare.15049140
title: Estimation of polymorphisms in the drug-metabolizing enzyme, cytochrome <i>P450 2C19</i> gene in six major ethnicities of Pakistan

description: Interindividual differences in cytochrome P450 (<i>CYP)</i> 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for <i>CYP2C19*2</i> and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for <i>CYP2C19*2</i> and 8.14% for CYP2C19*3. For <i>CYP2C19*2</i>, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for <i>CYP2C19*3</i>, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19.