cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.17892307
title: Transcription factor NFIC functions as a tumor suppressor in lung squamous cell carcinoma progression by modulating lncRNA CASC2

description: Nuclear factor I (NFI) family is emerging found playing oncogenic or tumor-suppressive potential in cancers. However, the function and underlying mechanisms of NFIC, in the progression of Lung Squamous Cell Carcinoma (LUSC) remain unclear. Therefore, this study aims to probe into the function of NFIC in the development of LUSC. In the present study, we reported that NFIC was low expressed in human LUSC tissues and cell lines. NFIC inhibited LUSC cell proliferation and promoted cell apoptosis <i>in vitro</i> and <i>in vivo</i>. Moreover, NFIC also inhibited LUSC cell migration and invasion. Furthermore, we found that there were binding sites between lncRNA cancer susceptibility candidate 2 (CASC2) and NFIC, whose relationship was confirmed by the luciferase reporter assay. The expression of CASC2 and the expression of NFIC were positively correlated, and the function of CASC2 overexpression is similar to that of NFIC overexpression, which suggested that CASC2 may play a key role in LUSC development. Our study provided a new perspective for NFIC acting as an antioncogene in LUSC tumorigenesis, and NFIC and CASC2 may serve as novel potential targets for the treatment of LUSC.
DOI: 10.6084/m9.figshare.17892307.v1
title: Transcription factor NFIC functions as a tumor suppressor in lung squamous cell carcinoma progression by modulating lncRNA CASC2

description: Nuclear factor I (NFI) family is emerging found playing oncogenic or tumor-suppressive potential in cancers. However, the function and underlying mechanisms of NFIC, in the progression of Lung Squamous Cell Carcinoma (LUSC) remain unclear. Therefore, this study aims to probe into the function of NFIC in the development of LUSC. In the present study, we reported that NFIC was low expressed in human LUSC tissues and cell lines. NFIC inhibited LUSC cell proliferation and promoted cell apoptosis <i>in vitro</i> and <i>in vivo</i>. Moreover, NFIC also inhibited LUSC cell migration and invasion. Furthermore, we found that there were binding sites between lncRNA cancer susceptibility candidate 2 (CASC2) and NFIC, whose relationship was confirmed by the luciferase reporter assay. The expression of CASC2 and the expression of NFIC were positively correlated, and the function of CASC2 overexpression is similar to that of NFIC overexpression, which suggested that CASC2 may play a key role in LUSC development. Our study provided a new perspective for NFIC acting as an antioncogene in LUSC tumorigenesis, and NFIC and CASC2 may serve as novel potential targets for the treatment of LUSC.
DOI: 10.6084/m9.figshare.17213003
title: Monoclonal antibodies to activated CDK4: use to investigate normal and cancerous cell cycle regulation and involvement of phosphorylations of p21 and p27

description: Cyclin-dependent kinase 4 (CDK4) is a master integrator that couples mitogenic/oncogenic signaling with the cell division cycle. It is deregulated in most cancers and inhibitors of CDK4 have become standard of care drugs for metastatic estrogen-receptor positive breast cancers and are being evaluated in a variety of other cancers. We previously characterized the T-loop phosphorylation at T172 of CDK4 as the highly regulated step that determines the activity of cyclin D-CDK4 complexes. Moreover we demonstrated that the highly variable detection of T172-phosphorylated CDK4 signals the presence or absence of the active CDK4 targeted by the CDK4/6 inhibitory drugs, which predicts the tumor cell sensitivity to these drugs including palbociclib. To date, the phosphorylation of CDK4 has been very poorly studied because only few biochemical techniques and reagents are available for it. In addition, the available ones including 2D-IEF separation of CDK4 modified forms are considered too tedious. The present report describes the generation, selection and characterization of the first monoclonal antibodies that specifically recognize the active CDK4 phosphorylated on its T172 residue. One key to this success was the immunization with a long phosphopeptide corresponding to the complete activation segment of CDK4. These monoclonal antibodies specifically recognize T172-phosphorylated CDK4 in a variety of assays, including western blotting, immunoprecipitation and, as a capture antibody, a sensitive ELISA from cell lysates. The specific immunoprecipitation of T172-phosphorylated CDK4 allowed to clarify the involvement of phosphorylations of co-immunoprecipitated p21 and p27, showing a privileged interaction of T172-phosphorylated CDK4 with S130-phosphorylated p21 and S10-phosphorylated p27.
 <b>Abbreviations</b>:
2D: two-dimensional; CAK: CDK-activating kinase; CDK: cyclin-dependent kinase; HAT: Hypoxanthine-Aminopterin-Thymidine; FBS: fetal bovine serum; IP: immunoprecipitation; ID: immunodetection; mAb: monoclonal antibody; PAGE: polyacrylamide gel electrophoresis; PBS: phosphate buffer saline; pRb: retinoblastoma susceptibility protein; SDS: sodium dodecyl sulfate; DTT: dithiotreitol; TET: tetracyclin repressor; Avi: Avi tag; TEV: tobacco etch virus cleavage site; EGFP: enhanced green fluorescent protein; BirA: bifunctional protein biotin ligase BirA; IRES: internal ribosome entry site; HIS: poly-HIS purification tag; DELFIA: dissociation-enhanced lanthanide fluorescent immunoassay; 3-MBPP1: 1-(1,1-dimethylethyl)-3[(3-methylphenyl) methyl]-1H-pyrazolo[3,4-d] pyrimidin-4-amine; BSA: bovine serum albumin; ECL: Enhanced chemiluminescence
DOI: 10.6084/m9.figshare.17129363
title: LncRNA ASB16-AS1 drives proliferation, migration, and invasion of colorectal cancer cells through regulating miR-185-5p/TEAD1 axis

description: As a common malignant tumor, colorectal cancer (CRC) has a high incidence. Recent investigations have suggested that although great improvement has been achieved in the survival rate of early-stage CRC patients, the overall survival rate remains low. Mounting reports have proved that lncRNAs take part in the development of various cancers and possess the regulatory functions in cancers. For example, ASB16 antisense RNA 1 (ASB16-AS1) is a poorly researched novel lncRNA whose specific functions in CRC are still unknown. In our research, we discovered that ASB16-AS1 was with high expression in CRC cells. In addition, ASB16-AS1 silencing restrained the proliferation, migration, invasion, and stemness while accelerating cell apoptosis of CRC cells. Mechanism experiments were applied to explore the regulatory mechanism of ASB16-AS1. It turned out that miR-185-5p could interact with ASB16-AS1 and inhibited the progression of CRC cells. TEAD1 (TEA domain transcription factor1) - a major effector of the Hippo signaling was proved to serve as the target of miR-185-5p and promote CRC development. In short, ASB16-AS1 drove the progression of CRC through the regulation of miR-185-5p/TEAD1 axis.
DOI: 10.6084/m9.figshare.17129363.v1
title: LncRNA ASB16-AS1 drives proliferation, migration, and invasion of colorectal cancer cells through regulating miR-185-5p/TEAD1 axis

description: As a common malignant tumor, colorectal cancer (CRC) has a high incidence. Recent investigations have suggested that although great improvement has been achieved in the survival rate of early-stage CRC patients, the overall survival rate remains low. Mounting reports have proved that lncRNAs take part in the development of various cancers and possess the regulatory functions in cancers. For example, ASB16 antisense RNA 1 (ASB16-AS1) is a poorly researched novel lncRNA whose specific functions in CRC are still unknown. In our research, we discovered that ASB16-AS1 was with high expression in CRC cells. In addition, ASB16-AS1 silencing restrained the proliferation, migration, invasion, and stemness while accelerating cell apoptosis of CRC cells. Mechanism experiments were applied to explore the regulatory mechanism of ASB16-AS1. It turned out that miR-185-5p could interact with ASB16-AS1 and inhibited the progression of CRC cells. TEAD1 (TEA domain transcription factor1) - a major effector of the Hippo signaling was proved to serve as the target of miR-185-5p and promote CRC development. In short, ASB16-AS1 drove the progression of CRC through the regulation of miR-185-5p/TEAD1 axis.
DOI: 10.6084/m9.figshare.20630002
title: Cancer-associated fibroblast-released extracellular vesicles carrying miR-199a-5p induces the progression of​ gastric cancer through regulation of FKBP5-mediated AKT1/mTORC1 signaling pathway

description: Accumulating evidence has unfolded the significance of extracellular vesicles (EVs) in diseases and cancers. Here, we attempted to discuss the role of cancer-associated fibroblasts (CAFs)-derived EVs containing miR-199a-5p in gastric tumorigenesis. Upregulated miR-199a-5p was first identified in cancer cells. Then, we selected CAFs for isolation of EVs which were co-cultured with AGS cells. We observed successful delivery of miR-199a-5p via CAF-derived EVs. Besides, miR-199a-5p promoted malignant properties of AGS cells. Moreover, miR-199a-5p downregulated FKBP5, leading to upregulated phosphorylation level of AKT1, which promoted the malignant phenotypes of AGS cells by activating mammalian target of rapamycin complex 1(mTORC1). Exosomal miR-199a-5p from CAFs promoted gastric tumorigenesis <i>in vivo</i>. Our findings point toward the critical role of CAFs-derived EVs carrying miR-199a-5p in gastric cancer progression.
DOI: 10.6084/m9.figshare.20630002.v1
title: Cancer-associated fibroblast-released extracellular vesicles carrying miR-199a-5p induces the progression of​ gastric cancer through regulation of FKBP5-mediated AKT1/mTORC1 signaling pathway

description: Accumulating evidence has unfolded the significance of extracellular vesicles (EVs) in diseases and cancers. Here, we attempted to discuss the role of cancer-associated fibroblasts (CAFs)-derived EVs containing miR-199a-5p in gastric tumorigenesis. Upregulated miR-199a-5p was first identified in cancer cells. Then, we selected CAFs for isolation of EVs which were co-cultured with AGS cells. We observed successful delivery of miR-199a-5p via CAF-derived EVs. Besides, miR-199a-5p promoted malignant properties of AGS cells. Moreover, miR-199a-5p downregulated FKBP5, leading to upregulated phosphorylation level of AKT1, which promoted the malignant phenotypes of AGS cells by activating mammalian target of rapamycin complex 1(mTORC1). Exosomal miR-199a-5p from CAFs promoted gastric tumorigenesis <i>in vivo</i>. Our findings point toward the critical role of CAFs-derived EVs carrying miR-199a-5p in gastric cancer progression.
DOI: 10.6084/m9.figshare.20479484
title: Upregulated miR-322-5p regulates cell cycle and promotes cell proliferation and apoptosis by directly targeting Wee1 in mice liver injury

description: Liver injury from any number of causes (e.g. chemical material, drugs and diet, viral infection) is a global health problem, and its mechanism is not clearly understood. MicroRNAs (miRNAs) expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and have also shown promise as biomarkers for disease. Previous studies reported the regulation effects of miRNAs in liver injury, whereas function and molecular mechanisms of miR-322-5p were still unclear. Therefore, our study focused on the biological role of miR-322-5p in carbon tetrachloride (CCl<sub>4</sub>)-induced liver injury proliferation, apoptosis, and cell cycle. A mouse model of CCl<sub>4</sub>-induced liver injury was established, and the transcriptomes and miRNAs transcriptomes of 2d and 5d liver tissues after injury were sequenced. The expression of miR-322-5p and the cell cycle genes were detected in liver tissues and Hepa1-6 cell line by miRNA RT-PCR, qRT-PCR. The effects of miR-322-5p on liver cell proliferation, cell cycle and apoptosis were evaluated using MTS assays and flow cytometry analysis. The relationship between miR-322-5p and Wee1 was predicted and confirmed by bioinformatics analysis and a dual luciferase reporter assay. Functional experiments, including an MTS assay and flow cytometric analysis, were performed to study the effects of Wee1. MiR-322-5p was upregulated in injury liver tissues, and downregulated miR-322-5p was proved to inhibit proliferation, apoptosis and arrest cell cycle at G2/M <i>in vitro</i>. The dual-luciferase reporter assay results indicated that miR-322-5p has a binding site at position 285 in the Wee1 3´UTR. The effects of miR-322-5p in proliferation and cell cycle regulation can be abolished by Wee1 through rescue experiments. By directly targeting Wee1 influenced the expression of several cell cycle factors, including Cyclin dependent kinase 1 (Cdk1), cyclin B1 (Ccnb1) and Cell division cyclin 25C (Cdc25C). MiR-322-5p may function as a suppressive factor by negatively controlling Wee1, thus, highlighting the potential role of miR-322-5p as a therapeutic target for liver injury. <b>Abbreviations:</b> ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione, γ-glutamyl cysteinel + glycine; CCl<sub>4</sub>: Carbon tetrachloride; HE: Haematoxylin and eosin; KEGG: Kyoto Encyclopedia of Genes and Genomes
DOI: 10.6084/m9.figshare.20410868
title: CTPS1 inhibition suppresses proliferation and migration in colorectal cancer cells

description: Colorectal cancer (CRC) is now the third most prevalent tumor and one of the deadliest cancers worldwide, with an increasing prevalence every year. Therefore, we urgently need to understand the mechanisms regulating the progression of colorectal cancer and find potential diagnostic biomarkers. In this study, we performed an analysis using the TCGA and GEO databases to find a molecular biomarker for the diagnosis of CRC, namely CTPS1. The results of this analysis revealed that CTPS1 could promote tumor proliferation and metastasis. Furthermore, bioinformatics analysis revealed that CTPS1 promoted CRC progression through cell cycle and p53 pathways. Further investigation demonstrated that CTPS1 might be involved in the regulation of CCNB1, RRM2, GTSE1, CDK2 and CHEK2 genes. Moreover, PCR confirmed that CTPS1 regulated GTSE1 and CDK2 molecules. Then, western blot was used to verify that CTPS1 promoted the expression of GTSE1 and CDK2 by inhibiting the expression of p53. In summary, we identified an important diagnostic biomarker for CRC, namely CTPS1, and its importance was validated at the cellular level. These results suggest that CTPS1 could serve as a candidate biomarker for CRC and CTPS1 inhibitors may be a potential treatment for CRC.
DOI: 10.6084/m9.figshare.20410868.v2
title: CTPS1 inhibition suppresses proliferation and migration in colorectal cancer cells

description: Colorectal cancer (CRC) is now the third most prevalent tumor and one of the deadliest cancers worldwide, with an increasing prevalence every year. Therefore, we urgently need to understand the mechanisms regulating the progression of colorectal cancer and find potential diagnostic biomarkers. In this study, we performed an analysis using the TCGA and GEO databases to find a molecular biomarker for the diagnosis of CRC, namely CTPS1. The results of this analysis revealed that CTPS1 could promote tumor proliferation and metastasis. Furthermore, bioinformatics analysis revealed that CTPS1 promoted CRC progression through cell cycle and p53 pathways. Further investigation demonstrated that CTPS1 might be involved in the regulation of CCNB1, RRM2, GTSE1, CDK2 and CHEK2 genes. Moreover, PCR confirmed that CTPS1 regulated GTSE1 and CDK2 molecules. Then, western blot was used to verify that CTPS1 promoted the expression of GTSE1 and CDK2 by inhibiting the expression of p53. In summary, we identified an important diagnostic biomarker for CRC, namely CTPS1, and its importance was validated at the cellular level. These results suggest that CTPS1 could serve as a candidate biomarker for CRC and CTPS1 inhibitors may be a potential treatment for CRC.
DOI: 10.6084/m9.figshare.20479484.v1
title: Upregulated miR-322-5p regulates cell cycle and promotes cell proliferation and apoptosis by directly targeting Wee1 in mice liver injury

description: Liver injury from any number of causes (e.g. chemical material, drugs and diet, viral infection) is a global health problem, and its mechanism is not clearly understood. MicroRNAs (miRNAs) expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and have also shown promise as biomarkers for disease. Previous studies reported the regulation effects of miRNAs in liver injury, whereas function and molecular mechanisms of miR-322-5p were still unclear. Therefore, our study focused on the biological role of miR-322-5p in carbon tetrachloride (CCl<sub>4</sub>)-induced liver injury proliferation, apoptosis, and cell cycle. A mouse model of CCl<sub>4</sub>-induced liver injury was established, and the transcriptomes and miRNAs transcriptomes of 2d and 5d liver tissues after injury were sequenced. The expression of miR-322-5p and the cell cycle genes were detected in liver tissues and Hepa1-6 cell line by miRNA RT-PCR, qRT-PCR. The effects of miR-322-5p on liver cell proliferation, cell cycle and apoptosis were evaluated using MTS assays and flow cytometry analysis. The relationship between miR-322-5p and Wee1 was predicted and confirmed by bioinformatics analysis and a dual luciferase reporter assay. Functional experiments, including an MTS assay and flow cytometric analysis, were performed to study the effects of Wee1. MiR-322-5p was upregulated in injury liver tissues, and downregulated miR-322-5p was proved to inhibit proliferation, apoptosis and arrest cell cycle at G2/M <i>in vitro</i>. The dual-luciferase reporter assay results indicated that miR-322-5p has a binding site at position 285 in the Wee1 3´UTR. The effects of miR-322-5p in proliferation and cell cycle regulation can be abolished by Wee1 through rescue experiments. By directly targeting Wee1 influenced the expression of several cell cycle factors, including Cyclin dependent kinase 1 (Cdk1), cyclin B1 (Ccnb1) and Cell division cyclin 25C (Cdc25C). MiR-322-5p may function as a suppressive factor by negatively controlling Wee1, thus, highlighting the potential role of miR-322-5p as a therapeutic target for liver injury. <b>Abbreviations:</b> ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione, γ-glutamyl cysteinel + glycine; CCl<sub>4</sub>: Carbon tetrachloride; HE: Haematoxylin and eosin; KEGG: Kyoto Encyclopedia of Genes and Genomes
DOI: 10.6084/m9.figshare.19097625.v1
title: TRPM2-AS promotes the malignancy of osteosarcoma cells by targeting miR-15b-5p/PPM1D axis

description: Osteosarcoma (OS) is a malignant tumor with a low survival rate and a high incidence rate worldwide. Although research has reported the involvement of long non-coding RNAs (lncRNAs) in the pathogenesis of OS cells, the role of TRPM2-AS, miR-15b-5p, and PPM1D in OS progression remains unclear. This study aimed to examine the interaction of the TRPM2-AS/miR-15b-5p/PPM1D axis in OS cells to gain new insights into the molecular mechanism and pathogenesis of OS. After performing <i>in vitro</i> functional assays, we discovered that TRPM2-AS was overexpressed in OS cells. TRPM2-AS silencing impaired OS cell viability, proliferation, and migration, while it induced apoptosis in OS cells <i>in vitro</i>. Our experimental analysis also revealed that PPM1D is a direct target of miR-15b-5p. TRPM2-AS silencing was found to reverse the tumorigenic effect of the miR-15b-5p inhibitor, while the miR-15b-5p inhibitor restored the inhibition of OS caused by silencing PPM1D. Moreover, our findings revealed that miR-15b-5p exerted its tumor-suppressive role by directly targeting PPM1D. In conclusion, this study suggests that TRPM2-AS could promote OS cell malignancy by sponging miR-15b-5p/PPM1D axis.
DOI: 10.6084/m9.figshare.20410868.v1
title: CTPS1 suppresses proliferation and migration in colorectal cancer cells

description: Colorectal cancer (CRC) is now the third most prevalent tumor and one of the deadliest cancers worldwide, with an increasing prevalence every year. Therefore, we urgently need to understand the mechanisms regulating the progression of colorectal cancer and find potential diagnostic biomarkers. In this study, we performed an analysis using the TCGA and GEO databases to find a molecular biomarker for the diagnosis of CRC, namely CTPS1. The results of this analysis revealed that CTPS1 could promote tumor proliferation and metastasis. Furthermore, bioinformatics analysis revealed that CTPS1 promoted CRC progression through cell cycle and p53 pathways. Further investigation demonstrated that CTPS1 might be involved in the regulation of CCNB1, RRM2, GTSE1, CDK2 and CHEK2 genes. Moreover, PCR confirmed that CTPS1 regulated GTSE1 and CDK2 molecules. Then, western blot was used to verify that CTPS1 promoted the expression of GTSE1 and CDK2 by inhibiting the expression of p53. In summary, we identified an important diagnostic biomarker for CRC, namely CTPS1, and its importance was validated at the cellular level. These results suggest that CTPS1 could serve as a candidate biomarker for CRC and CTPS1 inhibitors may be a potential treatment for CRC.
DOI: 10.6084/m9.figshare.19097625
title: TRPM2-AS promotes the malignancy of osteosarcoma cells by targeting miR-15b-5p/PPM1D axis

description: Osteosarcoma (OS) is a malignant tumor with a low survival rate and a high incidence rate worldwide. Although research has reported the involvement of long non-coding RNAs (lncRNAs) in the pathogenesis of OS cells, the role of TRPM2-AS, miR-15b-5p, and PPM1D in OS progression remains unclear. This study aimed to examine the interaction of the TRPM2-AS/miR-15b-5p/PPM1D axis in OS cells to gain new insights into the molecular mechanism and pathogenesis of OS. After performing <i>in vitro</i> functional assays, we discovered that TRPM2-AS was overexpressed in OS cells. TRPM2-AS silencing impaired OS cell viability, proliferation, and migration, while it induced apoptosis in OS cells <i>in vitro</i>. Our experimental analysis also revealed that PPM1D is a direct target of miR-15b-5p. TRPM2-AS silencing was found to reverse the tumorigenic effect of the miR-15b-5p inhibitor, while the miR-15b-5p inhibitor restored the inhibition of OS caused by silencing PPM1D. Moreover, our findings revealed that miR-15b-5p exerted its tumor-suppressive role by directly targeting PPM1D. In conclusion, this study suggests that TRPM2-AS could promote OS cell malignancy by sponging miR-15b-5p/PPM1D axis.