scholarly journals Bioinformatic Analysis Identifying S100a9 Associated With Cell Proliferation and Metastasis in Neuroblastoma

2021 ◽  
Author(s):  
Xian Chen ◽  
Yukun Xue ◽  
Jiao Feng ◽  
Qingwu Tian ◽  
Yunyuan Zhang ◽  
...  
Keyword(s):  
Distant Metastases ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
Molecular Networks ◽  
Migration And Invasion ◽  
Ppi Network ◽  
Metastatic Relapse ◽  
Network Identification ◽  
Prediction Of Metastasis

Abstract Background: More than half of neuroblastoma (NB) patients presented with distant metastases and the mortality of patients suffering from metastatic relapse was about 90%. It is urgent to find a biomarker that can facilitate the prediction of metastasis in NB patients. Methods and Results: In the present study, we systematically analyzed Gene Expression Omnibus (GEO) datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NB. We found totally, 176 up-regulated and 19 down-regulated differentially expressed genes (DEGs) were identified. Based on these DEGs, a PPI network composed of 150 nodes and 452 interactions was established. PPI network identification combined with qRT-PCR, ELISA and IHC, S100A9 as was screened as an outstanding gene. Furthermore, in vitro tumorigenesis assays demonstrated that S100A9 overexpression enhanced the proliferation, migration, and invasion of NB cells. Conclusions: Taken together, our findings suggested that S100A9 could participate in NB tumorigenesis and metastasis and that S100A9 has the potential to be used as a biomarker in the prediction of NB metastasis.

scholarly journals Identification S100A9 as a potential biomarker in neuroblastoma

2021 ◽  
Author(s):  
Xian Chen ◽  
Yukun Xue ◽  
Jiao Feng ◽  
Qingwu Tian ◽  
Yunyuan Zhang ◽  
...  
Keyword(s):  
Distant Metastases ◽  
Gene Expression Omnibus ◽  
Molecular Networks ◽  
Migration And Invasion ◽  
Ppi Network ◽  
Potential Biomarker ◽  
Tumorigenesis And Progression ◽  
Network Identification ◽  
Prediction Of Metastasis

Abstract Background More than half of Neuroblastoma (NB) patients presented with distant metastases and the relapse of metastatic patients was up to 90%. It is urgent to explore a biomarker that could facilitate the prediction of metastasis in NB patients. Methods and results In the present study, we systematically analyzed Gene Expression Omnibus datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NB metastasis. In total, 176 up-regulated and 19 down-regulated differentially expressed genes (DEGs) were identified. Based on these DEGs, a PPI network composed of 150 nodes and 452 interactions was established. Through PPI network identification combined with qRT-PCR, ELISA and IHC, S100A9 was screened as an outstanding gene. Furthermore, in vitro tumorigenesis assays demonstrated that S100A9 overexpression enhanced the proliferation, migration and invasion of NB cells. Conclusions Taken together, our findings suggested that S100A9 could participate in NB tumorigenesis and progression. In addition, S100A9 has the potential to be used as a promising clinical biomarker in the prediction of NB metastasis.

scholarly journals circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Sen Wang ◽  
Dong Tang ◽  
Wei Wang ◽  
Yining Yang ◽  
Xiaoqing Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioinformatic Analysis ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Genome Wide ◽  
Proliferation And Metastasis

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

scholarly journals Circular RNA _0008278 acts as a sponge of miR-378 and promotes proliferation and metastasis in gastric cancer

2021 ◽  
Author(s):  
Xuan Li ◽  
Haisheng Qian ◽  
Hao Dong ◽  
Yini Dang ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioinformatic Analysis ◽  
Potential Method ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Regulatory Molecule

Abstract Background: Circular RNA (circRNA) is rising as an indispensable regulatory molecule in the progression of various kinds of malignant growth. However, little is known about the capacity and instruments of circRNA_0008727 in gastric cancer (GC). Our point was to recognize a novel circRNA-microRNA-mRNA useful system in gastric cancer. Method: CircRNA_0008278 was identified in three paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circRNA_0008278 combined with in vitro and in vivo assays were performed to prove the functional significance of circRNA_0008278. The molecular mechanism of circRNA_0008278 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments.Results: CircRNA_0008278 was frequently upregulated in GC tissues, and high circRNA_0008278 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circRNA_0008278 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, circRNA_0008278 over-expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circRNA_0008278 could sponge miR-378, thus indirectly regulating theYY1 expression and contributing to GC tumourigenesis.Conclusion: Our findings demonstrate that circRNA_0008278 functions as a tumour promoter in GC, and a new pathway circRNA_0008278/miR-378/YY1 which may be potential method for gastric cancer treatment.

scholarly journals CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Dandan Li ◽  
Jiawei Zhang ◽  
Jing Yang ◽  
Jie Wang ◽  
Runling Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Epithelial To Mesenchymal Transition ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Mesenchymal Transition

AbstractCircRNA mitochondrial tRNA translation optimization 1 (circMTO1) functions as a tumor suppressor usually and is related to the progression of many tumors, including hepatocellular carcinoma (HCC). CircMTO1 is downregulated in HCC as compared to adjacent nontumor tissue, which may suppress the HCC progression by certain signal pathways. However, the underlying signal pathway remains largely unknown. The interactions between circMTO1 and miR-541-5p were predicted through bioinformatics analysis and verified using pull-down and dual-luciferase reporter assays. CCK-8, transwell, and apoptosis assays were performed to determine the effect of miR-541-5p on HCC progression. Using bioinformatic analysis, dual-luciferase reporter assay, RT-qPCR, and western blot, ZIC1 was found to be the downstream target gene of miR-541-5p. The regulatory mechanisms of circMTO1, miR-541-5p, and ZIC1 were investigated using in vitro and in vivo rescue experiments. The results depicted that silencing circMTO1 or upregulating miR-541-5p expression facilitated HCC cell proliferation, migration, and invasion and inhibited apoptosis. CircMTO1 silencing upregulated the expression of downstream ZIC1 regulators of the Wnt/β-catenin pathway markers, β-catenin, cyclin D1, c-myc, and the mesenchymal markers N-cadherin, Vimentin, and MMP2, while the epithelial marker E-cadherin was downregulated. MiR-541-5p knockdown had the opposite effect and reversed the effect of circMTO1 silencing on the regulation of downstream ZIC1 regulators. Intratumoral injection of miR-541-5p inhibitor suppressed tumor growth and reversed the effect of circMTO1 silencing on the promotion of tumor growth in HCC. These findings indicated that circMTO1 suppressed HCC progression via the circMTO1/ miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling and epithelial-to-mesenchymal transition, making it a novel therapeutic target.

scholarly journals Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Donglan Huang ◽  
Qianqian Liu ◽  
Weijun Zhang ◽  
Chunyue Huang ◽  
Ronghui Zheng ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Prognostic Indicator ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Functional Verification ◽  
Data Sets ◽  
Hub Genes ◽  
Data Set ◽  
Blue Module

Abstract Background Despite improvements in nasopharyngeal carcinoma (NPC) treatment, patients with recurrence and metastasis still have a poor prognosis. Thus, the identification of novel biomarkers is urgently needed to predict outcomes and tailor treatment for NPC. Methods Four data sets were downloaded from Gene Expression Omnibus, and one data set GSE68799 of which was applied to filtrate key modules and hub genes by construction of a co-expression network. Other data sets (GSE12452 and GSE53819) were used to verify hub genes. The data set GSE102349 was devoted to identify prognostic hub genes by survival analysis. To explored whether prognostic hub genes are related to hypoxia signatures in NPC, correlation analysis was carried out, and followed by functional verification experiments of those genes in vitro. Results By co-expression network analysis, blue module was regarded as a key module in the benign and malignant group, and IGSF9 of the blue module was identified as a prognostic hub gene. Moreover, IGSF9 is expected to be a innovative hypoxia-related gene in NPC based on the strong associativity between expression of IGSF9 and hypoxia scores of three signatures (99-gene, 26-gene and 15-gene). Further functional studies verified that down-regulated expression of IGSF9 could reduce the proliferation, migration and invasion ability of NPC cells, and hypoxia could induce the expression of IGSF9. Conclusion IGSF9 was identified to be relevant to prognosis and involved in hypoxia in NPC. IGSF9 might serve as one novel prognostic indicator of NPC in the future.

scholarly journals TROAP Promotes Breast Cancer Proliferation and Metastasis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Kai Li ◽  
Ruo Zhang ◽  
Minjie Wei ◽  
Li Zhao ◽  
Yu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Critical Role ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Cancer Proliferation ◽  
Expression Levels ◽  
Microtubular Cytoskeleton ◽  
Mrna And Protein Expression

Trophinin-associated protein (TROAP) is a cytoplasmic protein required for microtubular cytoskeleton regulation and spindle assembly, and its expression plays a critical role in the initiation and progression of various types of cancer. However, little is known about the role of TROAP in breast cancer (BC). TROAP mRNA expression levels and clinical data from Gene Expression Omnibus (GEO) datasets (GSE42568, 104 BC patients; GSE1456, 159 BC patients; and GSE21653, 266 BC patients) were analyzed by the R2: Genomics Analysis and Visualization Platform to estimate overall survival (OS). We also analyzed the genes correlated with TROAP by gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to predict potential relationships between TROAP and other genes in BC. Our study verified that both TROAP mRNA and protein expression levels were upregulated in human BC samples and cell lines. In vitro experiments demonstrated that TROAP knockdown significantly inhibited cell proliferation, the G1 to S phase transition, and the migration and invasion abilities of BC cells. The present study suggests that TROAP plays an important role in promoting the proliferation, invasion, and metastasis of BC.

scholarly journals Long Noncoding RNA Linc00152 Functions as a Tumor Propellant in Pan-Cancer

2017 ◽  
Vol 44 (6) ◽  
pp. 2476-2490 ◽  
Author(s):  
Shouping Xu ◽  
Lin Wan ◽  
Huizi Yin ◽  
Hongbiao Xu ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Dna Hypomethylation ◽  
Normal Tissues ◽  
Super Enhancer ◽  
Pan Cancer

Background/Aims: The oncogenic role of linc00152 in pan-cancer is unclear. Methods: In this study, RNA-Seq of 33 breast specimens was performed, and the expression of linc00152 was validated by qPCR using 50 paired breast cancer tissues and adjacent normal tissues. This result combined with the expression of linc00152 in pan-cancer was revalidated by Gene Expression Omnibus and The Cancer Genome Atlas data. Next, the oncogenic roles of linc00152 in view of prognosis, chemoresistance, genomic and epigenetic regulation, including DNA methylation and histone modification, potential biological function enrichment, and basic molecular function in pan-cancer, were also evaluated in vitro and in vivo. Results: Linc00152 is upregulated in pan-cancer, especially in progressive cancer, and the high expression of linc00152 may lead to a worse prognosis and chemoresistance in pan-cancer patients. Amplification, DNA hypomethylation, promoter-like lncRNA characteristics and super-enhancer regulation are the drivers that lead to the upregulation of linc00152 in pan-cancer. Meanwhile, linc00152 was involved in cancer-related pathways, infection and immune response-associated pathways by enriched analysis using TCGA data. Finally, linc00152 was confirmed to promote the proliferation, migration and invasion in MDA-MB-231, SGC-7901 and 786-O. Moreover, RIP and RNA pull-down assays indicated that linc00152 can bind to EZH2 directly. Conclusion: All of the results indicated that linc00152 acted as an oncogenic propellant from various perspectives, and it may be an effective therapy target in pan-cancer.

scholarly journals EGR1 Modulated LncRNA HNF1A-AS1 Drives Glioblastoma Progression Via miR-22-3p/ENO1 Axis

2021 ◽  
Author(s):  
Chunchun Ma ◽  
Hongliang Wang ◽  
Gang Zong ◽  
Jie He ◽  
Yuyang Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Regulation Mechanism ◽  
Functional Studies

Abstract Background: Accumulating evidences revealed that long noncoding RNAs (lncRNAs) have been participated in cancer malignant progression, including glioblastoma multiforme (GBM). Despite much studies have found the precise biological role in the regulatory mechanisms of GBM，however the molecular mechanisms，particularly upstream mechanisms still need further elucidated. Methods: RT-QPCR, cell transfection, western blotting and bioinformatic analysis were executed to detect the expression of EGR1, HNF1A-AS1, miR-22-3p and ENO1 in GBM. Cell proliferation assay, colony formation assay, wound healing, migration and invasion assays were performed to detect the malignant characters of GBM cell. The molecular regulation mechanism was confirmed by luciferase reporter assay, ChIP and RIP. Finally, orthotopic mouse models were established to examine the effect of HNF1A-AS1 in vivo.Results: In the current study, we analyzed clinical samples to show that the long non-coding antisense transcript of HNF1A, HNF1A-AS1, is upregulated and associated with poor prognosis in GBM. Functional studies revealed that knockdown of HNF1A-AS1 markedly inhibits cell proliferation, migration and invasion both in vitro and in vivo, whereas overexpression of HNF1A-AS1 exerts opposite effect. Mechanistically, the transcription factor EGR1 forced the transcription of HNF1A-AS1 by directly binding the promoter region of HNF1A-AS1. Furthermore, combined bioinformatics analysis with our mechanistic work, using luciferase reporter assays and RIP, we first demonstrated that HNF1A-AS1 functions as a competing endogenous RNA (ceRNA) with miR-22-3p to regulate ENO1 expression in GBM cells. HNF1A-AS1 directly binds to miR-22-3p and significantly inhibits miR-22-3p expression, while ENO1 expression was increased. miR-22-3p inhibitor offsets the HNF1A-AS1 silencing induced suppression in proliferation, migration and invasion of GBM cells, as well as promotion effect on ENO1 expression. ENO1 was verified as a direct target of miR-22-3p and its expression levels was negatively with the prognosis in GBM patients. Conclusion: Taken together, our study illuminated the definite mechanism of HNF1A-AS1 in promoting GBM malignancy, and provided a novel therapeutic target for further clinical application.

scholarly journals Association between SNAP25 and human glioblastoma multiform: a comprehensive bioinformatic analysis

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Cheng Yu ◽  
Jianxing Yin ◽  
Xiefeng Wang ◽  
Lijiu Chen ◽  
Yutian Wei ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Proportional Hazards ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
Cox Proportional Hazards ◽  
Venn Diagram ◽  
Ppi Network ◽  
Hub Gene ◽  
Protein Protein Interaction ◽  
Gated Channel

Abstract Background: Glioblastoma multiforme (GBM) is a most common aggressive malignant brain tumor. In recent years, targeted therapy has been increasingly applied in GBM treatment. Methods: In the present study, GSE22866 was downloaded from gene expression omnibus (GEO). The genomic and clinical data were obtained from TCGA. The differentially expressed genes (DEGs) were identified and functional analysis was performed using clusterprofiler. Then, the co-expression network for the DEGs was established using the “WGCNA” package. Next, the protein–protein interaction (PPI) was assessed using Search Tool for the Retrieval of Interacting Genes Database (STRING) and hub modules in Cytoscape were screened. The Venn diagram was plotted to showcase the overlapped hub DEGs in PPI network and TCGA. Univariate and multivariate Cox proportional hazards regression analyses were performed to predict the risk score of each patient. Validations of the hub gene were completed in other databases. Results: Functional analysis of the DEGs verified the involvement of DEGs in growth factor binding and gated channel activity. Among the 10 GBM-related modules, the red one displayed the strongest tie with GBM. VAMP2 was filtered out as the most intimate protein. The PPI network and TCGA were comprehensively analyzed. Finally, SNAP25 was identified as a real hub gene positively correlated with GBM prognosis. The result was validated by GEPIA, ONCOMINE database and qRT-PCR. Conclusions: SNAP25 might act as a GBM suppressor and a biomarker in GBM treatment.

scholarly journals RNA methylation-mediated LINC01559 suppresses colorectal cancer progression by regulating the miR-106b-5p/PTEN axis

2021 ◽  
Author(s):  
Ke Shi ◽  
Shuaixi Yang ◽  
Quanbo Zhou ◽  
Chen Chen ◽  
Bo Shao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
In Situ Hybridization ◽  
Noncoding Rnas ◽  
Bioinformatic Analysis ◽  
Migration And Invasion ◽  
Sequencing Analysis ◽  
Rna Methylation

Abstract BackgroundLong noncoding RNAs (lncRNAs) regulate multiple biological effects in cancers. Recently, RNA methylation has been found to modify not only coding RNAs but also some noncoding RNAs. How RNA methylation affects lncRNAs to affect colorectal cancer (CRC) progression remains elusive.MethodsRNA-sequencing of cancer and normal tissues was analysed. LINC01559 in CRC was selected and verified by western blot (WB), quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Functional experiments in vitro and in vivo were used to explore the biological functions of LINC01559 in CRC. The LINC01559/miR-106-5p/PTEN axis was explored at different levels of analysis, including fluorescence in situ hybridization (FISH), luciferase assays, and rescue experiments. RIP-sequencing, m6A RNA immunoprecipitation (MeRIP) assays and bioinformatic analysis were conducted to determine the upstream mechanism of LINC01559.ResultsLINC01559, identified by RNA-sequencing analysis, was downregulated in CRC tissues and cell lines compared with normal controls. Lower expression of LINC01559 in CRC patients predicted a poor prognosis. In addition, PTEN was found to be positively correlated with LINC01559, and bioinformatic analysis and in vitro experiments indicated that miR-106b-5p could be the link between LINC01559 and PTEN. Then, downregulated LINC01559 restored the malignant phenotype of CRC cells in vivo and in vitro, while cotransfection of si-LINC01559 and miR-106b-5p inhibitor neutralized this effect. Notably, METTL3 was found to be highly expressed in CRC, and the downregulation of METTL3 could inhibit the migration and invasion of CRC cells. Mechanistically, we found abundant m6A modification sites on LINC01559. Then, we uncovered these sites as potential targets of METTL3 through experiments in vivo.ConclusionThe results revealed a negative functional regulation of LINC01559/miR-106b-5p/PTEN axis in CRC progression, and explored a new mechanism of METTL3-mediated m6A modification on LINC01559 formation. These results elucidate a novel potential therapeutic target for CRC treatment.Trial registrationThe human cancer tissues used in this study were approved by Ethnics Committee of The First Affiliated Hospital of Zhengzhou University in December 19, 2019, and the TRN is 2019-KW-423.

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