bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALDOLASE A regulates invasion of bladder cancer cells via E‐cadherin‐EGFR signaling
Authors: Li Jianwei , Wang Fang , Gao Hongzhi , Huang Sihuai , Cai Fangzhen , Sun Jianguo 
Published: May 2019

AbstractGlycolysis and glycogenesis are known to be tightly associated with cancer cell migration. However, their roles in bladder cancer have not been reported. In this study, ALDOLASE A (ALDOA) was identified in a coexpression network generated using glycolysis‐ and glycogenesis‐related genes in Kyoto Encyclopedia of Genes and Genomes. ALDOA was located in the central region in the network, and the cancer genome atlas (TCGA) data suggest that ALDOA expression levels are associated with viability in patients with cancer at the middle and late stages. Bladder cancer cell lines, T24 and RT4, were used to knockdown (sh) or overexpress (OE) ALODA to analyze its role. The sh‐ALDOA reduced cell viability, colony formation rate, and invasion cell number; while OE had an opposite effect compared with sh‐ALDOA. Further, the sh‐ALDOA expression induced E‐cadherin level while reduced N‐cadherin and vimentin levels. The OE cells reduced E‐cadherin and induced N‐cadherin and vimentin levels. In addition, epidermal growth factor receptor (EGFR), mitogen‐activated protein kinase (MAPK), and AKT serine/threonine kinase (AKT) phosphorylation levels are all reduced in sh‐ALODA while activated in OE cells compared with the control group. But either sh‐ALODA or OE did not change total protein levels of EGFR, MAPK, and AKT. To further analyze E‐cadherin function in ALDOA regulation on bladder cancer cells, sh‐ALDOA and sh‐E‐cadherin were cotransfected in T24 and RT4 cells. The results indicated that sh‐ALDOA and sh‐E‐cadherin expressions eliminated sh‐ALDOA function, resulting similar cell viability, colony formation rate, and invasion cell number with control group. Also, sh‐ALDOA and shE‐cadherin expressions increased EGFR, MAPK, and AKT phosphorylation levels; and the levels were similar to the control group. But, sh‐ALDOA and sh‐E‐cadherin expressions did not change N‐cadherin and vimentin levels, which maintain similar levels with sh‐ALDOA‐expressing cells. Taken together, these results suggest that ALDOA might play an important function in bladder cancer and its action may be though E‐cadherin‐EGFR signaling.
LINC00339 regulates ROCK1 by miR‐152 to promote cell proliferation and migration in hepatocellular carcinoma
Authors: Chen Kun , Zhang Liang 
Published: May 2019

AbstractBackground/AimsEmerging evidence have demonstrated that long noncoding RNAs are involved in the development and metastasis of various cancers including hepatocellular carcinoma (HCC). However, the role of LINC00339 in HCC progression is still unknown.MethodsThe LINC00339 expression in HCC cancer cells (HUH7, HepG2, HUH‐6, and SK‐Hep‐1) and tissues was assessed by quantitative real‐time polymerase chain reaction (qRT‐PCR). Functional experiments including cell counting Kit‐8 wound‐healing assay and transwell assay were used to explore the cell proliferation, migration, and invasion, respectively. The related molecular mechanisms were determined by Western blot. The RNA pull‐down assay, luciferase reporters assay, qRT‐PCR, and Western blot were performed to explore and confirm the interaction between LINC00339 and miR‐152, between miR‐152 and ROCK1. The role of LINC00339 in tumor formation and metastasis were explored through in vivo experiments.ResultsLINC00339 was highly expressed in HCC tissues and cell lines. LINC00339 promoted the cell proliferation, migration, and invasion of HCC cells, while knockout of LINC00339 showed the opposite trends. The proliferation and migration of HCC cells induced by LINC00339 overexpression were mostly reversed after transfected with miR‐152 mimics. LINC00339 exerted oncogenesis effect on HCC progression by targeting miR‐152/ROCK1, and the expression of LINC00339 was negatively correlated with miR‐152 expression and positively correlated with ROCK1 expression in clinical HCC samples. Moreover, we also proved that LINC00339 overexpression exacerbated the tumor formation and metastases in nude mice and LINC00339 silence showed the opposite results.ConclusionLINC00339 might act as a potential therapeutic target for HCC.
UCP2 protect the heart from myocardial ischemia/reperfusion injury via induction of mitochondrial autophagy
Authors: Wu Hui , Ye Ming , Liu Di , Yang Jian , Ding Jia‐wang , Zhang Jing , Wang Xin‐an , Dong Wu‐song , Fan Zhi‐xing , Yang Jun 
Published: May 2019

AbstractUncoupling protein 2 (UCP2), located in the mitochondrial inner membrane, is a predominant isoform of UCP that expressed in the heart and other tissues of human and rodent tissues. Nevertheless, its functional role during myocardial ischemia/reperfusion (I/R) is not entirely understood. Ischemic preconditioning (IPC) remarkably improved postischemic functional recovery followed by reduced lactate dehydrogenase (LDH) release with simultaneous upregulation of UCP2 in perfused myocardium. We then investigated the role of UCP2 in IPC‐afforded cardioprotective effects on myocardial I/R injury with adenovirus‐mediated in vivo UCP2 overexpression (AdUCP2) and knockdown (AdshUCP2). IPC‐induced protective effects were mimicked by UCP2 overexpression, while which were abolished with silencing UCP2. Mechanistically, UCP2 overexpression significantly reinforced I/R‐induced mitochondrial autophagy (mitophagy), as measured by biochemical hallmarks of mitochondrial autophagy. Moreover, primary cardiomyocytes infected with AdUCP2 increased simulated ischemia/reperfusion (sI/R)‐induced mitophagy and therefore reversed impaired mitochondrial function. Finally, suppression of mitophagy with mdivi‐1 in cultured cardiomyocytes abolished UCP2‐afforded protective effect on sI/R‐induced mitochondrial dysfunction and cell death. Our data identify a critical role for UCP2 against myocardial I/R injury through preventing the mitochondrial dysfunction through reinforcing mitophagy. Our findings reveal novel mechanisms of UCP2 in the cardioprotective effects during myocardial I/R.
Microarray analysis of long‐noncoding RNAs and mRNA expression profiles in human steroid‐induced avascular necrosis of the femoral head
Authors: Luo Hongbin , Lan Weibin , Li Yongfeng , Lian Xiaolan , Zhang Nanwen , Lin Xinhua , Chen Peng 
Published: May 2019

AbstractThis study performed the first microarray analysis of long‐noncoding RNA (lncRNA) and mRNA expression profiles in human steroid‐induced avascular necrosis of the femoral head (SAVNFH). Expression levels of lncRNAs and mRNAs in three human SAVNFH samples and three human femoral head fracture samples (controls) were detected using third‐generation lncRNA microarrays (KangChen Biotech, Shanghai, China). The fold change, false discovery rate, and P value were utilized to filter genes with significant differential expression in the SAVNFH samples compared with the control samples. In total, there were 1179 upregulated and 3214 downregulated lncRNAs (P2. zerofold, P < 0.05). Meanwhile, 1092 upregulated and 565 downregulated mRNAs were found in the SAVNFH samples compared with the control samples. Then, quantitative real‐time polymerase chain reaction was used to confirm the previous microarray results using 8 and 20 selected dysregulated lncRNAs and mRNAs, respectively, and the results generally confirmed the microarray findings. Finally, we used Gene Ontology (GO) and pathway analysis to investigate the functions of the altered mRNAs and their associated GO terms and biological pathways. The Immune system process term (GO:0002376) was the most significantly upregulated GO term, and the Regulation of blood coagulation term (GO:0030193) was the most significantly downregulated GO term in the biological process category for the SAVNFH samples. “Hematopoietic cell lineage ‐ Homo sapiens (human) (Pathway ID: hsa04640)” and “Complement and coagulation cascades ‐ Homo sapiens (human) (Pathway ID: hsa04610)” were the most significantly up‐ and downregulated pathways in the SAVNFH samples compared with the controls. In conclusion, the differential expression of lncRNAs and mRNAs may be correlated with the pathogenesis of SAVNFH, and these significantly dysregulated lncRNAs and mRNAs may function through networks or participate in several specific biological processes. Further research is needed to understand their exact functions and mechanisms in SAVNFH.
Serum miR‐515‐3p, a potential new RNA biomarker, is involved in gastric carcinoma
Authors: Han Xue , Li Xing , Zhao Hengyu , Zhou Danyang , Sun Banghao , Liu Anqi , Zhang Jianan , Cui Zhongqi , Ma Xiaoyu , Yuan Lijie 
Published: May 2019

AbstractObjectivesmicroRNAs (miRNAs) have provided a new opportunity for developing diagnostic biomarkers and effective therapeutic targets in gastric cancer (GC). In this study, we aimed to investigate the relationship between miR‐515‐3p and GC development.Experimental DesignThe Gene Expression Omnibus (GEO) database was used for screening genes and miRNA and for 2R analysis. miRNA prediction target genes and screening key genes were analyzed using protein interactions (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of miRNA‐mRNA interactions was predicated by Cytoscape (v.3.5.1), Institute of Systems Biology & University of California, San Diego & Pasteur institute & University of California, San Francisco. Finally, miR‐515‐3p levels were detected by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) in gastric cells and plasma levels. Then, the association between the expression level of miR‐515‐3p and the clinicopathological features of patients with GC was further analyzed.Observations and ConclusionsWe found that miR‐515‐3p was markedly overexpressed in individuals with GC compared with that in normal gastric cells (NCs) and the surgery group (P < 0.0001). In addition, receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) value of 0.8555 for miR‐515‐3p.SignificanceOur results present new information to the field of gastric cancer and has done a good job of creating an initial hypothesis using the database as well as validate their initial results. These results suggest that serum miR‐515‐3p is a novel potential biomarker for the detection of GC.
Gene regulation analysis of the effects of evodiamine on tongue squamous cell carcinoma
Authors: Wu Yuyan , Wang Jing , Zhao Jiayuan , Zhang Yunxia , Sun Yunjie , Chen Jian , Wang Jing 
Published: May 2019

AbstractObjectiveTo use gene chip technology to study the effects of evodiamine (EVO) on the gene expression profile of tongue squamous cell carcinoma (TSCC) CAL‐27 cell line, for the purpose of analyzing the mechanisms underlying the effects of EVO on gene expression and functional regulation of TSCC cells at the gene level.MethodDifferentially expressed genes in CAL‐27 cells treated with EVO were detected using gene chip technology and analyzed using ingenuity pathway analysis.ResultsMicroarray results showed that there were 1243 differentially expressed genes following treatment with CAL‐27 cells; 684 genes were upregulated and 559 were downregulated. Classical pathway analysis revealed a total of 89 signal transduction pathways with upregulated gene set enrichment, including lipopolysaccharide/interleukin (IL)‐1‐mediated inhibition of retinoid X receptor (RXR) function, agrin interactions at neuromuscular junctions, cholecystokinin/gastrin‐mediated signaling, toll‐like receptor signaling, and IL‐6 signaling. A total of 39 signal transduction pathways were enriched for the downregulated genes, including interferon signals, liver X receptor/RXR activation signals, and RhoGDI signals. In the disease and function analysis, the upregulated genes were enriched in viral infection, RNA virus replication, viral replication, cancer cell invasion, cell invasion, and other related functions, while downregulated genes were enriched in neuromuscular diseases, and leukocyte differentiation, antiviral response, connective tissue cell death and other functions.ConclusionsGene chip analysis offers an effective means of screening differential gene expression between EVO‐treated TSCCs and controls, thus providing a sound basis for further research.
Overlapped differentially expressed genes between acute lymphoblastic leukemia and chronic lymphocytic leukemia revealed potential key genes and pathways involved in leukemia
Authors: Zhang Suwei , Zhang Qiaoxin , Yin Jun , Wu Xianheng 
Published: May 2019

AbstractCommon differentially expressed genes (DEGs) in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) might play critical roles in the pathogenesis and process of leukemia. We collected RNA sequencing (RNA‐seq) data of human CLL, ALL samples, and normal peripheral blood CD19+ B cells as well as thymus samples, and analyzed similarities and differences between their transcriptomes using Cuffdiff2, DESeq, and edgeR. Compared with the RNA‐seq data of normal peripheral blood CD19+ B cells and thymus samples, there were a large number of DEGs in ALL and CLL. DEGs in ALL and CLL not only have their distinguished features but also have a similar pattern. To figure out the common DEGs between CLL and ALL, we further identified 26 overlapped genes between CLL and ALL, among which 10 genes showed similar expression variation profiles whereas 16 genes showed opposite variation. The expression levels of 10 genes (SCML4, TNF‐α, CD1C, FGFR1, MYO7B, DUSP1, PAP1GAP, MAN1C1, SLFN5, and CD8A) among the 26 genes were further confirmed by experiments, which was consistent with the results obtained by analyzing the RNA‐seq data. The current study contributes to better understanding the pathophysiology of leukemia and unearthing novel potential prognostic markers and therapeutic targets of leukemia.
Partial reprogramming as a therapeutic approach for heart disease: A state‐of‐the‐art review
Authors: Talkhabi Mahmood 
Published: May 2019

AbstractHeart disease such as myocardial infarction is the first cause of mortality in all countries. Today, cardiac cell‐based therapy using de novo produced cardiac cells is considered as a novel approach for cardiac regenerative medicine. Recently, an alchemy‐like approach, known as direct reprogramming or direct conversion, has been developed to directly convert somatic cells to cardiac cells in vitro and in vivo. This cellular alchemy is a short‐cut and safe strategy for generating autologous cardiac cells, and it can be accomplished through activating cardiogenesis‐ or pluripotency‐related factors in noncardiac cells. Importantly, pluripotency factors‐based direct cardiac conversion, known as partial reprogramming, is shorter and more efficient for cardiomyocyte generation in vitro. Today, this strategy is achievable for direct conversion of mouse and human somatic cells to cardiac lineage cells (cardiomyocytes and cardiac progenitor cells), using transgene free, chemical‐based approaches. Although, heart‐specific partial reprogramming seems to be challenging for in vivo conversion of cardiac fibroblasts to cardiac cells, but whole organism‐based in vivo partial reprogramming ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in mouse. Notably, cardiac cells produced using partial reprogramming strategy can be a useful platform for disease modeling, drug screening and cardiac cell‐based therapy, once the safety issues are overcome. Herein, we discuss about all progresses in de novo production of cardiac cells using partial reprogramming‐based direct conversion, as well as give an overview about the potential applications of this strategy in vivo and in vitro.
Identification of aberrantly methylated differentially expressed genes in breast cancer by integrated bioinformatics analysis
Authors: Yi Lilan , Luo Peng , Zhang Jian 
Published: May 2019

AbstractBackgroundAbnormal DNA methylation has been demonstrated to drive breast cancer tumorigenesis. Thus, this study aimed to explore differentially expressed biomarkers driven by aberrant methylation in breast cancer and explore potential pathological mechanisms using comprehensive bioinformatics analysis.MethodsGene microarray datasets of expression (GSE45827) and methylation (GSE32393) were extracted from the Gene Expression Omnibus database. Abnormally methylated differentially expressed genes (DEGs) were obtained by overlapping datasets. Functional enrichment analysis of screened genes and protein‐protein interaction (PPI) networks were executed with the Search Tool for the Retrieval of Interacting Genes database. PPI networks were visualized, and hub genes were screened using Cytoscape software. The results were further verified using Oncomine and The Cancer Genome Atlas (TCGA) databases. Finally, the genetic alterations and prognostic roles of hub genes were analyzed.ResultsIn total, we found 18 hypomethylated upregulated oncogenes and 21 hypermethylated downregulated tumor suppressor genes (TSGs). These genes were mainly linked to the biological process categories of cellular component movement and cellular metabolism as well as nuclear factor‐κB (NF‐κB) and ataxia telangiectasia mutated (ATM) signaling pathways. Six hub genes were identified: three hypomethylated upregulated oncogenes (BCL2, KIT, and RARA) and three hypermethylated downregulated TSGs (ATM, DICER1, and DNMT1). The expression and methylation status of hub genes validated in Oncomine and TCGA databases were significantly altered and were consistent with our findings. Downregulation of BCL2, KIT, ATM, and DICER1 was closely associated with shorter overall survival in breast cancer patients. In addition, the expression levels of ATM and DICER1 were significantly distinct among different subgroups of clinical stages, molecular subtypes, and histological types.ConclusionsOur study reveals possible methylation‐based DEGs and involved pathways in breast cancer, which could provide novel insights into underlying pathogenesis mechanisms. Abnormally methylated oncogenes and TSGs, especially ATM and DICER1, may emerge as novel biomarkers and therapeutic targets for breast cancer in the future.
LOC103691336/miR‐138‐5p/BMPR2 axis modulates Mg‐mediated osteogenic differentiation in rat femoral fracture model and rat primary bone marrow stromal cells
Authors: Li Ding , Yu Kun , Xiao Tao , Dai Yilong , Liu Lihong , Li Hui , Jiang Dayue , Xiong Liang 
Published: May 2019

AbstractIntramedullary stabilization is frequently used to treat long bone fractures. Since implant removal can become technically very challenging with the potential to cause further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)‐based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. Herein, the degradation of Mg and steel implants, the pathological characteristics and osteoblast differentiation in mice femora were examined. To investigate the molecular mechanism, we analyzed the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in Mg‐implanted or stain‐steel‐implanted callus tissues. lncRNA LOC103691336 was upregulated in Mg‐implanted tissues and most relevant to BMPR2, a kinase receptor of BMPs with an established role in osteogenesis. The knockdown of LOC103691336 attenuated Mg‐mediated osteogenic differentiation. Furthermore, miR‐138‐5p, previously reported to inhibit osteogenic differentiation, could bind to LOC103691336 and BMPR2 in bone marrow stromal cells (BMSCs). LOC103691336 competed with BMPR2 for miR‐138‐5p binding in BMSCs to attenuate the inhibitory effect of miR‐138‐5p on BMPR2 expression. Finally, the effect of LOC103691336 knockdown on Mg‐mediated osteogenic differentiation could be attenuated by miR‐138‐5p inhibition. In conclusion, we provided a novel mechanism of Mg implants mediating the osteogenesis differentiation and demonstrated that Mg implants may be promising for improving fracture healing.
Integrated analysis of transcriptome data revealed MMP3 and MMP13 as critical genes in anaplastic thyroid cancer progression
Authors: Ma Yuehua , Cang Shundong , Li Guoqing , Su Yong , Zhang Huifeng , Wang Limin , Yang Junpeng , Shi Xiaoyang , Qin Guijun , Yuan Huijuan 
Published: May 2019

AbstractTo better understand the molecular mechanisms of anaplastic thyroid carcinoma (ATC), we aimed to identify the hub genes specifically involved in ATC by integrated bioinformatics analysis. In this study, using three Gene Expression Omnibus data sets with the same platform GPL570, we screened hub genes involved in ATC progression. In vitro experiments, such as western blot analysis, Transwell assays, and coimmunoprecipitation, was performed to verify our findings. By comparing three subtypes of thyroid cancer with normal tissue, we found ATC harbored more changed genes than well and poorly differentiated thyroid cancer. Using specifically differentially expressed genes between ATC and normal thyroid tissues to perform Gene ontology (GO) analysis, ATC showed enrichments of GO terms involved in lymphocyte migration and activation, collagen catabolic and metabolic process, thyroid hormone synthesis, and embolism. Using genes involved in extracellular matrix, coexpression network analysis and protein–protein interaction analysis were performed to identify matrix metalloproteinase 3 (MMP3) and MMP13 as two hub genes. Our experimental data indicated that both MMP3 and MMP13 were upregulated in ATC and knockdown of either of them could notably suppress ATC cell invasion and migration. Mechanistically, Gene Set Enrichment Analysis, coimmunoprecipitation, and rescue experiments revealed MMP3 and MMP13 not only interacted with each other, but also regulated each other through the janus kinase/signal transducer and activator of transcription 3 and mammalian target of rapamycin pathways. In conclusion, we identified a specific molecular mechanisms for the development of ATC by integrated analysis of transcriptome and in vitro experiments, which suggested that MMP3 and MMP13 might be developed as novel therapeutic targets for ATC.
Characterization of hepatitis delta virus strains spreading in Abuja, Nigeria
Authors: Ifeorah Ijeoma M. , Faleye Temitope O. C. , Bakarey Adeleye S. , Adewumi Olubusuyi M. , Gerber Athenais , Le Gal Frédéric , Adeniji Johnson A. , Gordien Emmanuel , Onyemelukwe Ngozi F. 
Published: May 2019

AbstractHepatitis delta virus (HDV) is responsible for the most severe form of liver disease in humans. So far, eight genotypes (HDV‐1 to ‐8) have been individualized worldwide. Little is known about HDV strains that spread in Nigeria. HDV genotyping was performed in 15 anti–HDV positive samples from a cohort of 306 hepatitis B virus (HBV)‐infected patients in Abuja (Nigeria). Phylogenetic analyses revealed 90% were HDV‐1, two among them clustering with European/Asian HDV‐1, the remaining one being HDV‐6. It was also found that two members of a couple superinfected with the same HDV strain, were enveloped by two different HBV strains of genotype E.