Dataset Information

The downregulated long noncoding RNA DHRS4-AS1 is protumoral and associated with the prognosis of clear cell renal cell carcinoma.

ABSTRACT: Background:Long noncoding RNAs (lncRNAs) have been identified as important factors in cancer biology and are deregulated in many cancers. The present study aimed to determine the expression and roles of lncRNA DHRS4-AS1 in the progression of clear cell renal cell carcinoma (ccRCC). Methods and results:Using high-throughput RNA-sequencing data of ccRCC tumors from the Cancer Genome Atlas project, we identified lncRNA DHRS4-AS1 as significantly associated with ccRCC patients' overall survival. We confirmed the downregulation of DHRS4-AS1 in ccRCC by assessing its expression levels in a cohort of 52 tumor and paired non-tumor samples. In addition, we found that low DHRS4-AS1 expression was significantly associated with a high tumor node metastasis stage, lymph node metastasis, advanced pathological grade and poor prognosis. Furthermore, DHRS4-AS1 overexpression inhibited the progression of cell cycles of ccRCC in vitro. These data indicate that DHRS4-AS1 functions by preventing the proliferation and invasion, inhibiting the cell cycle progression and promoting the apoptosis of ccRCC cells. Conclusion:Taken together, our findings identify the role of DHRS4-AS1 as a tumor inhibitor in ccRCC for the first time, demonstrating that DHRS4-AS1 is a potential prognostic biomarker that could potentially be applied in ccRCC therapy.

SUBMITTER: Wang C

PROVIDER: S-EPMC6141115 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The downregulated long noncoding RNA <i>DHRS4-AS1</i> is protumoral and associated with the prognosis of clear cell renal cell carcinoma.

Wang Changlin C Wang Gang G Zhang Zijian Z Wang Zichun Z Ren Minghua M Wang Xiaoxiong X Li Haoming H Yu Yipeng Y Liu Jing J Cai Licheng L Li Yong Y Zhang Daming D Zhang Cheng C

OncoTargets and therapy 20180910

<h4>Background</h4>Long noncoding RNAs (lncRNAs) have been identified as important factors in cancer biology and are deregulated in many cancers. The present study aimed to determine the expression and roles of lncRNA <i>DHRS4-AS1</i> in the progression of clear cell renal cell carcinoma (ccRCC).<h4>Methods and results</h4>Using high-throughput RNA-sequencing data of ccRCC tumors from the Cancer Genome Atlas project, we identified lncRNA <i>DHRS4-AS1</i> as significantly associated with ccRCC pa ...[more]

PMID: 30254456

Similar Datasets

Project description:BackgroundThe long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC).MethodsThe expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo.ResultsIn this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo.ConclusionsTaken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.

Project description:BackgroundNecroptosis has been found to be associated with tumorigenesis and tumor progression. However, the prognostic effect of long noncoding RNAs (lncRNAs) associated with necroptosis in clear cell renal cell carcinoma (ccRCC) is still unclear.MethodsPearson correlation analysis was used to identify necroptosis-related genes and lncRNAs obtained from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression analyses were used to identify a novel necroptosis-associated lncRNAs signature that significantly correlated with survival of ccRCC. Next, single sample gene set enrichment analysis (ssGSEA) was employed to assess the extent of infiltration with immune cells. Analyses to predict the half-maximal inhibitory concentration (IC50) of patients in different risk groups were also conducted. Moreover, follow-up data of an immunotherapy cohort were used to test for differences in the immunotherapeutic efficiency between two risk groups. Finally, patients with ccRCC were divided into two groups based on 6 prognostic lncRNAs.ResultsWe developed a signature of necroptosis-related lncRNAs, which was verified as an independent prognostic factor that can predict prognosis up to 7 years. Patients with higher risk scores were shown to have higher immune suppressive cell infiltration levels and expression of immune checkpoint genes, which suggests that these patients were in a state of immunosuppression. Patients in the low-risk group were found to have an increased response to immunotherapy. A prognostic prediction nomogram was conducted to predict long-term survival of patients. Cluster A tumors were considered hot tumors, since they were correlated with higher levels of immune infiltration and were more sensitive to immunotherapy.ConclusionsA comprehensive bioinformatics analysis was conducted, which found that the necroptosis-associated lncRNA signature might be a potent prognostic factor for patients with ccRCC, which could contribute to improved prognosis of these patients.

Project description:Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The "CIBERSORT" R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-β secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis.

Project description:BackgroundClear cell renal cell carcinoma (RCC) is the most common subtype of RCC. Although targeted therapy can provide superior treatment outcomes, it is prone to drug resistance, and individual responses to immunotherapy vary greatly. Therefore, finding new diagnostic and therapeutic targets for RCC is of considerable importance. Long noncoding RNA (lncRNA) GPRC5D-AS1 can serve as a biomarker in clinical applications and the prognosis of lung squamous cell carcinoma. However, the specific mechanism of action of lncRNA GPRC5D-AS1 in RCC has not yet been clarified. Therefore, this paper explores the expression of lncRNA GPRC5D-AS1 in the renal cancer cell line 786-0, and conducts a preliminary study of its molecular mechanism. Selecting nude mice for tumor experiments is because of the high genomic and physiological similarity between mice and humans. Conducting tumor research on mice allows for better control of experimental conditions, aiding researchers in more accurately observing and analysing tumor characteristics and responses.MethodsSmall interfering RNA (siRNA) and plasmid cloning DNA (pcDNA) 3.1 were used to transfect renal cancer cell line 786-0 to silence and overexpress the lncRNA GPRC5D-AS1 gene. Quantitative real-time fluorescence polymerase chain reaction was used to detect the difference in lncRNA GPRC5D-AS1 expression in blank control group, negative control group, siGPRC5D-AS1 group and oeGPRC5D-AS1 group. The effects of silence and overexpression of lncRNA GPRC5D-AS11 on the proliferation of 786-0 cells were detected in cell colony formation experiments; the changes in the migration and invasion of 786-0 cells were detected via cell scratch assay and transwell assay, respectively; the differences in tumor growth between groups were determined via tumorigenesis experiments in nude mice; and the expression of proliferation-related protein [β-catenin, Ki67 and proliferating cell nuclear antigen (PCNA)] and invasion-related protein (N-cadherin and E-cadherin) were detected via Western blotting.ResultsCompared with blank control group and negative control group, the siGPRC5D-AS1 group showed a significant decrease in the relative expression of lncRNA GPRC5D-AS1 (P<0.05), a significant increase in the number of proliferating cells and migrating cells (P<0.05), a significant increase in the tumor volume of nude mice (P<0.05), a significant increase in β-catenin, Ki67, PCNA and N-cadherin protein expression (P<0.05), and a significant decrease in E-cadherin protein expression (P<0.05); conversely, these results were opposite for the eGPRC5D-AS1 group.ConclusionsSilencing the expression of lncRNA GPRC5D-AS1 can enhance the proliferation, invasion, and migration ability of renal cancer cell line 786-0, which can be weakened by the overexpression of lncRNA GPRC5D-AS1.

Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is characterized by the accumulation of lipid-reactive oxygen species. Ferroptosis, due to the lipid peroxidation, has been reported to be strongly correlated with tumorigenesis and progression. However, the functions of the ferroptosis process in ccRCC remain unclear.MethodsAfter sample cleaning, data integration, and batch effect removal, we used the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases to screen out the expression and prognostic value of ferroptosis-related lncRNAs and then performed the molecular subtyping using the K-means method. Then, the functional pathway enrichment and immune microenvironment infiltration between the different clusters were carried out. The results showed a significant difference in immune cell infiltration between the two clusters and the associated marker responded to individualized differences in treatment. Then, least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish a prognostic signature based on 5 lncRNAs. This signature could accurately predicted patient prognosis and served as an independent clinical risk factor. We then combined significant clinical parameters in multivariate Cox regression and the prognostic signature to construct a clinical predictive nomogram, which provides appropriate guidance for predicting the overall survival of ccRCC patients.ResultsThe prognostic differentially expressed ferroptosis-related LncRNAs (DEFRlncRNAs) were found, and 5 lncRNAs were finally used to establish the prognostic signature in the TCGA cohort, with subsequently validation in the internal and external cohorts. Moreover, we conducted the molecular subtyping and divided the patients in the TCGA cohort into two clusters showing differences in Hallmark pathways, immune infiltration, immune target expression, and drug therapies. Differences between clusters contributed to individualizing treatment. Furthermore, a nomogram was established to better predict the clinical outcomes of the ccRCC patients.ConclusionsOur study conducted molecular subtyping and established a novel predictive signature based on the ferroptosis-related lncRNAs, which contributed to the prognostic prediction and individualizing treatment of ccRCC patients.

Dataset Information

The downregulated long noncoding RNA DHRS4-AS1 is protumoral and associated with the prognosis of clear cell renal cell carcinoma.

Publications

The downregulated long noncoding RNA <i>DHRS4-AS1</i> is protumoral and associated with the prognosis of clear cell renal cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

The downregulated long noncoding RNA DHRS4-AS1 is protumoral and associated with the prognosis of clear cell renal cell carcinoma.

Publications

The downregulated long noncoding RNA &lt;i&gt;DHRS4-AS1&lt;/i&gt; is protumoral and associated with the prognosis of clear cell renal cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The downregulated long noncoding RNA <i>DHRS4-AS1</i> is protumoral and associated with the prognosis of clear cell renal cell carcinoma.