scholarly journals Novel miRNA Predicts Survival and Prognosis of Cholangiocarcinoma Based on RNA-seq Data and In Vitro Experiments

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Yuan Yao ◽  
Dechao Jiao ◽  
Zaoqu Liu ◽  
Jianjian Chen ◽  
Xueliang Zhou ◽  
...  
Keyword(s):  
Differential Expression ◽  
Target Genes ◽  
Cox Regression ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
In Vitro Experiments ◽  
Diagnosis And Prognosis ◽  
Novel Mirna ◽  
And Migration

Accumulating evidence has demonstrated that microRNAs (miRNAs or miRs) play an important role in the diagnosis and prognosis of tumors. In the case of cholangiocarcinoma (CCA), miRNAs may serve as potential tumor biomarkers and therapeutic targets. Based on The Cancer Genome Atlas (TCGA) database, fold change >2 was used to screen out miRNAs with differential expression in patients with CCA. Univariate and multivariate Cox regression analyses identified miR-3913-5p as an independent prognostic factor in patients with CCA. Overall survival and progression-free survival of patients with CCA were analyzed based on clinical data from TCGA database. In addition, four datasets were combined to identify 21 possible target genes of miR-3913, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to predict potential pathways and functions of the molecular target genes. Subsequently, the miRNAs associated with survival were selected to build the miRNA-mRNA expression network. Furthermore, the differential expression of miR-3913-5p in CCA cells and normal bile duct epithelial cells was confirmed through in vitro experiments. The possible target genes (RNF24 and SIGLEC) were further screened by reverse transcription-quantitative PCR. In addition, functional experiments showed that miR-3913-5p might be an oncogene that affects the proliferation and migration of CCA cells by inhibiting and mimicking miR-3913-5p. Therefore, miR-3913 may serve as a biomarker for the diagnosis and prognosis of patients with CCA.

scholarly journals MiR-1301-3p Inhibits Epithelial-mesenchymal Transition via Targeting RhoA in Pancreatic Cancer

2021 ◽  
Author(s):  
Xinxue Zhang ◽  
Zhangyong Ren ◽  
Junming Xu ◽  
Qing Chen ◽  
Jun Ma ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
And Migration

Abstract Micro(mi)RNAs play an essential role in the epithelial-mesenchymal transition (EMT) process in human cancers. This study aimed to uncover the regulatory mechanism of miR-1301-3p on EMT in pancreatic cancer (PC). The miRNA profilings from Gene Expression Omnibus datasets (GSE31568, GSE41372, and GSE32688) demonstrated the downregulation of miR-1301-3p in PC tissues, which was validated with 72 paired PC tissue samples through qRT-PCR detection. The low level of miR-1301-3p was associated with a poor prognosis for PC patients from the PC cohort of The Cancer Genome Atlas and the validation cohort. Gene Ontology analyses indicated that the target genes of miR-1301-3p were involved in cell cycle and adherent junction regulation. In vitro assays revealed that miR-1301-3p suppressed the proliferation and migration abilities of PC cells. Western blotting and luciferase reporter assays suggested that miR-1301-3p inhibited RhoA expression by targeting its 3′-untranslated region; RhoA upregulated N-cadherin and vimentin level, however, downregulated E-cadherin level. In conclusion, our study showed that miR-1301-3p could serve as a prognostic biomarker for PC and suppress PC cell malignancy by targeting RhoA induced EMT process.

scholarly journals The LncRNA NEAT1 Accelerates Lung Adenocarcinoma Deterioration and Binds to Mir-193a-3p as a Competitive Endogenous RNA

2018 ◽  
Vol 48 (3) ◽  
pp. 905-918 ◽  
Author(s):  
Dan-dan Xiong ◽  
Zu-yun Li ◽  
Lu Liang ◽  
Rong-quan He ◽  
Fu-chao Ma ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Target Genes ◽  
Biological Effects ◽  
Lung Epithelial Cells ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Normal Lung ◽  
In Vitro Experiments ◽  
Reporter Assay

Background/Aims: Long noncoding RNAs (lncRNAs) contribute to the development of multiple malignant tumors. Here, we focused on the biological function and underlying molecular mechanism of an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1), in lung adenocarcinoma (LUAD). Methods: In vitro experiments were conducted to determine the biological effects of NEAT1 in LUAD cells. A luciferase activity reporter assay was performed to corroborate the interaction between NEAT1 and miR-193a-3p. Data from Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA), and our in-house reverse transcription quantitative PCR (RT-qPCR) were combined to examine the expression of NEAT1 and miR-193a-3p in LUAD. To further explore the regulatory mechanism of NEAT1, we searched for putative target genes of miR-193a-3p from 12 online prediction databases and determined genes positively correlated with NEAT1 as candidate targets. Furthermore, we analyzed the expression of these selected genes using data from TCGA. Results: In vitro experiments showed that knockdown of NEAT1 in LUAD cells markedly restrained cell proliferation, invasion, and migration and stimulated cell apoptosis. The dual-luciferase reporter assay demonstrated that miR-193a-3p directly targeted NEAT1 at its 3’-UTR. We then detected NEAT1 and miR-193a-3p in LUAD cells and normal lung epithelial cells and discovered high expression of NEAT1 and low expression of miR-193a-3p in LUAD cell lines. Simultaneously, the pooled results from the GEO, Oncomine, TCGA, and in-house RT-qPCR showed that the NEAT1 expression increased while the miR-193a-3p expression decreased in LUAD tissues versus normal lung tissues. Furthermore, the USF1 gene was not only upregulated in LUAD, but also positively correlated with NEAT1, suggesting that NEAT1 may function as a ceRNA to sponge miR-193a-3p and abrogate the inhibitory effect of miR-193a-3p on USF1. Conclusions: Our findings indicate that NEAT1 plays important roles in the occurrence and progression of LUAD. It may exert its role by acting as a ceRNA to regulate miR-193a-3p.

scholarly journals The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zhang ◽  
Zhaohui Zhong ◽  
Mei Li ◽  
Jingyi Chen ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Actin Dynamics ◽  
Elevated Expression ◽  
Sw480 Cells ◽  
And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

scholarly journals Screening the genome for HCC-specific CpG methylation signatures as biomarkers for diagnosis and prognosis evaluation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Rui-kun Zhang ◽  
Jia-lin Liu
Keyword(s):  
Cox Regression ◽  
Malignant Tumors ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Survival Prediction ◽  
Training Set ◽  
Cpg Sites ◽  
Diagnosis And Prognosis ◽  
Patient Prognosis ◽  
Prognosis Evaluation

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and invasive malignant tumors in the world. The change in DNA methylation is a key event in HCC. Methods Methylation datasets for HCC and 17 other types of cancer were downloaded from The Cancer Genome Atlas (TCGA). The CpG sites with large differences in methylation between tumor tissues and paracancerous tissues were identified. We used the HCC methylation dataset downloaded from the TCGA as the training set and removed the overlapping sites among all cancer datasets to ensure that only CpG sites specific to HCC remained. Logistic regression analysis was performed to select specific biomarkers that can be used to diagnose HCC, and two datasets—GSE157341 and GSE54503—downloaded from GEO as validation sets were used to validate our model. We also used a Cox regression model to select CpG sites related to patient prognosis. Results We identified 6 HCC-specific methylated CpG sites as biomarkers for HCC diagnosis. In the training set, the area under the receiver operating characteristic (ROC) curve (AUC) for the model containing all these sites was 0.971. The AUCs were 0.8802 and 0.9711 for the two validation sets from the GEO database. In addition, 3 other CpG sites were analyzed and used to create a risk scoring model for patient prognosis and survival prediction. Conclusions Through the analysis of HCC methylation datasets from the TCGA and Gene Expression Omnibus (GEO) databases, potential biomarkers for HCC diagnosis and prognosis evaluation were ascertained.

scholarly journals A prospective study revealing the role of an immune-related eRNA, WAKMAR2, in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Linbang Wang ◽  
Jingkun Liu ◽  
Jiaojiao Tai ◽  
Nian Zhou ◽  
Tianji Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Pearson Correlation ◽  
Tumour Microenvironment ◽  
The Cancer Genome Atlas ◽  
Mcf7 Cells ◽  
Tumour Immunity ◽  
Immune Genes ◽  
Normal Tissues

AbstractEnhancer RNAs (eRNAs) are a subclass of non-coding RNAs that are generated during the transcription of enhancer regions and play an important role in tumourigenesis. In this study, we focused on the crucial eRNAs that participate in immune responses in invasive breast cancer (IBC). We first used The Cancer Genome Atlas and Human enhancer RNA Atlas to screen for tissue-specific eRNAs and their target genes. Through Pearson correlation analysis with immune genes, the eRNA WAKMAR2 was identified as a key candidate involved in IBC. Our further research suggested that WAKMAR2 is crucial in regulating the tumour microenvironment and may function by regulating immune-related genes, including IL27RA, RAC2, FABP7, IGLV1-51, IGHA1, and IGHD. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of WAKMAR2 in IBC and normal tissues, and the effect of WAKMAR2 on the regulation of downstream genes in MB-231 and MCF7 cells was studied in vitro. WAKMAR2 was found to be highly involved in tumour immunity and was downregulated in IBC tissues. Furthermore, the expression of WAKMAR2 and its target genes was observed at the pan-cancer level. This study provides evidence to suggest new potential targets for the treatment of breast cancer.

Immune Characteristics-Related Typing of Colorectal Cancer and the Establishment of 14-Gene Prognostic Model

2021 ◽  
Author(s):  
Jianxing Ma ◽  
Chen Wang
Keyword(s):  
Colorectal Cancer ◽  
Risk Model ◽  
Cox Regression ◽  
Nonnegative Matrix ◽  
Test Group ◽  
Progression Free Survival ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Immune Related Genes

Abstract This study is to establish NMF (nonnegative matrix factorization) typing related to the tumor microenvironment (TME) of colorectal cancer (CRC) and to construct a gene model related to prognosis to be able to more accurately estimate the prognosis of CRC patients. NMF algorithm was used to classify samples merged clinical data of differentially expressed genes (DEGs) of TCGA that are related to the TME shared in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and survival differences between subtype groups were compared. By using createData Partition command, TCGA database samples were randomly divided into train group and test group. Then the univariate Cox analysis, Lasso regression and multivariate Cox regression models were used to obtain risk model formula, which is used to score the samples in the train group, test group and GEO database, and to divide the samples of each group into high-risk and low-risk groups, according to the median score of the train group. After that, the model was validated. Patients with CRC were divided into 2, 3, 5 subtypes respectively. The comparison of patients with overall survival (OS) and progression-free survival (PFS) showed that the method of typing with the rank set to 5 was the most statistically significant (p=0.007, p<0.001, respectively). Moreover, the model constructed containing 14 immune-related genes (PPARGC1A, CXCL11, PCOLCE2, GABRD, TRAF5, FOXD1, NXPH4, ALPK3, KCNJ11, NPR1, F2RL2, CD36, CCNF, DUSP14) can be used as an independent prognostic factor, which is superior to some previous models in terms of patient prognosis. The 5-type typing of CRC patients and the 14 immune-related genes model constructed by us can accurately estimate the prognosis of patients with CRC.

scholarly journals Hypermethylation of APC2 Is a Predictive Epigenetic Biomarker for Chinese Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yuan He ◽  
Li-Yue Sun ◽  
Jing Wang ◽  
Rui Gong ◽  
Qiong Shao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Sequencing Analysis ◽  
Primary Tumors ◽  
Protein Levels ◽  
Normal Tissues ◽  
Ffpe Tissues ◽  
Epigenetic Biomarker

Objective. To investigate methylation of the adenomatosis polyposis coli homologue (APC2) promoter and its correlation with prognostic implications in Chinese colorectal cancer (CRC). Methods. The mRNA expression of APC2 in colorectal tissues was evaluated using the database of The Cancer Genome Atlas (TCGA). Methylation analysis of APC2 in tumor (n=66) and corresponding adjacent formalin-fixed and paraffin-embedded (FFPE) tissues (n=44) was performed by Sequenom EpiTYPER® and verified by cloning-based bisulfite sequencing analysis. Demethylation and retrieval of APC2 expression in cell lines HT29, HCT116, and SW480 were treated with 5-aza-2′-deoxycytidine (5-AZC). Results. Analysis of TCGA showed that APC2 mRNA was significantly downregulated in primary tumors when compared to normal tissues (p<0.05). APC2 methylation was upregulated (43.93% vs 7.31%, p<0.05) in tumors compared to adjacent FFPE tissues. In vitro experiments demonstrated that 5-AZC downregulated the methylation of APC2 and retrieved its expression of mRNA and protein levels (p<0.05). Multivariate Cox regression indicated that APC2_CPG_14 was an independent risk factor for overall survival (HR = 6.38, 95% CI: 1.59–25.64, p<0.05). Conclusion. This study indicates that APC2 is hypermethylated and may be a tumorigenesis biomarker for Chinese CRC patients.

scholarly journals Ferroptosis-Related Long Non-Coding RNAs and the Roles of LASTR in Stomach Adenocarcinoma

2021 ◽  
Author(s):  
Gongjun Wang ◽  
Libin Sun ◽  
Shasha Wang ◽  
Jing Guo ◽  
Hui Li ◽  
...  
Keyword(s):  
Cox Regression ◽  
Comprehensive Evaluation ◽  
Progression Free Survival ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Sequencing Data ◽  
Regulatory Relationship ◽  
Data Resource ◽  
Stomach Adenocarcinoma

Abstract Background: Ferroptosis is a form of cell death involved in diverse physiological context. Increasing evidence suggests that there is a closely regulatory relationship between ferroptosis and long noncoding RNAs (lncRNAs).Method: RNA-sequencing data from The Cancer Genome Atlas (TCGA) data resource and ferroptosis-related genes from FerrDb (http://www.zhounan.org/ferrdb/) data resource were employed to select differentially expressed lncRNAs. We performed Univariate Cox regression and multivariate Cox analyses analysis on these differentially expressed lncRNAs to screen independent predictive factors. Subsequently, we established two signatures for predicting overall survival (OS) and progression-free survival (PFS). Finally, experiments were conducted to verify the roles of LASTR in gastric cancer (GC).Results: We identified 12 differentially expressed lncRNAs linked with OS and 13 associated with PFS. Kaplan-Meier(K-M) analyses exhibited that the high-risk group was related to a poor prognosis of stomach adenocarcinoma (STAD). The AUCs of the OS, as well as PFS signatures of lncRNAs were 0.734 and 0.771, respectively, indicating their excellent efficacy in predicting STAD prognosis. Our experimental results illustrated that the inhibition of LASTR inhibited tumor proliferation and migration in GC.Conclusion: This comprehensive evaluation of the ferroptosis-related lncRNA landscape in STAD unearthed novel lncRNAs related to carcinogenesis. In addition, we also experimentally confirmed the effects of LASTR on proliferation, migration and ferroptosis. These results provide potential novel targets for tumor treatment and promote personalized medicine.

Abstract 101: MiR-4260 Promotes the Proliferation, Migration, and Tube Formation of Human Umbilical Vein Endothelial Cells

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Qi Sun ◽  
Dongcao Lv ◽  
Qiulian Zhou ◽  
Yihua Bei ◽  
Junjie Xiao
Keyword(s):  
Endothelial Cells ◽  
Target Genes ◽  
Cell Function ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Endothelial Cell Function ◽  
Human Umbilical Vein ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells

MicroRNAs (miRNAs, miRs), endogenous small non-coding RNA, have been shown to act as essential regulators in angiogenesis which plays important roles in improving blood flow and cardiac function following myocardial infarction. The current study investigated the potential of miR-4260 in endothelial cell function and angiogenesis using human umbilical vein endothelial cells (HUVEC). Our data demonstrated that overexpression of miR-4260 was associated with increased proliferation and migration of HUVEC using EdU incorporation assay (17.25%±1.31 vs 25.78%±1.24 in nc-mimics vs miR-4260 mimics, respectively) and wound healing assay, respectively. While downregulation of miR-4260 inhibited the proliferation (17.90%±1.37 vs 10.66%±1.41 in nc-inhibitor vs miR-4260 inhibitor, respectively) and migration of HUVEC. Furthermore, we found that miR-4260 mimics increased (129.75±3.68 vs 147±3.13 in nc-mimics vs miR-4260 mimics, respectively), while miR-4260 inhibitor decreased the tube formation of HUVECs in vitro (123.25±2.17 vs 92±4.45 in nc-inhibitor vs miR-4260 inhibitor expression, respectively). Our data indicate that miR-4260 contributes to the proliferation, migration and tube formation of endothelial cells, and might be essential regulators for angiogenesis. Further study is needed to investigate the underlying mechanism that mediates the role of miR-4260 in angiogenesis by identifying its putative downstream target genes.

FBXW7γ is a tumor-suppressive and prognosis-related FBXW7 transcript isoform in ovarian serous cystadenocarcinoma

2020 ◽  
Vol 16 (25) ◽  
pp. 1921-1930
Author(s):  
Zhou Xu ◽  
Lin Zhuang ◽  
Xiaoyin Wang ◽  
Qianrong Li ◽  
Yan Sang ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
In Vivo Studies ◽  
Protein Coding ◽  
Serous Cystadenocarcinoma ◽  
Skov3 Cells ◽  
Cancer Genome Atlas

Aim: To explore FBXW7 protein-coding transcript isoform (α, β and γ) expression, their functions and prognostic value in ovarian serous cystadenocarcinoma (OSC). Materials & methods: FBXW7 transcript data were collected from The Cancer Genome Atlas and the Genotype-Tissue Expression project. IOSE, A2780 and SKOV3 cells were used for in vitro and in vivo studies. Results: FBXW7α and FBXW7γ are dominant protein-coding transcripts that were downregulated in OSC. FBXW7γ overexpression reduced the protein expression of c-Myc, Notch1 and Yap1 and suppressed OSC cell growth in vitro and in vivo. FBXW7γ expression was an independent indicator of longer disease-specific survival (HR: 0.588; 95% CI: 0.449–0.770) and progression-free survival (HR: 0.708; 95% CI: 0.562–0.892). Conclusion: FBXW7γ is a tumor-suppressive and might be the only prognosis-related FBXW7 transcript in OSC.

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