Dataset Information

CircUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis.

ABSTRACT: We previously showed that microRNA-182 (miR-182) might promote cell proliferation and migration in triple-negative breast cancer (TNBC). This study aimed to investigate circular RNAs (circRNAs) that interact with miR-182 and play important roles in TNBC. Thirty patients with TNBC were enrolled. One pair of tumor and adjacent tissue samples (control) were submitted for circRNA sequencing to establish the expression profile of circRNAs. Concomitantly, circRNAs aberrantly expressed between TNBC and control groups were identified, and these differentially expressed circRNAs (DEcircRNAs) were subjected to Gene Ontology and KEGG pathway enrichment analyses, as well as prediction of interactions with miRNAs. The expression levels of 5 circRNAs interacting with miR-182 were validated using qRT-PCR. Associations between the expression of circUSP42 and clinicopathological features and prognosis were evaluated. A total of 825 upregulated and 1127 downregulated DEcircRNAs were identified between tumor and control groups. Upregulated DEcircRNAs were significantly involved in proteoglycans in cancer, and endocytosis. Downregulated DEcircRNAs were involved in the pathway of resistance to EGFR tyrosine kinase inhibitors. Prediction of circRNA-miRNA interactions showed that hsa_circ_0002032, chr6:131973682-132047340+, hsa_circ_0005982, hsa_circ_0007823 (circUSP42), and hsa_circ_0001777 might act as miRNA sponges for miR-182. qRT-PCR showed consistent results with circRNA sequencing data (P < 0.05). Downregulation of circUSP42 was significantly associated with lymph node metastasis (P?=?0.005) and advanced clinical stage (P?=?0.032). Furthermore, Kaplan-Meier plots showed that low expression of circUSP42 was closely associated with poor outcome (log-rank test, P < 0.001). Our data suggested that dysregulation of circUSP42 might contribute to the development and progression of TNBC.

SUBMITTER: Yu J

PROVIDER: S-EPMC7502800 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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circUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis.

Yu Jinling J Shen Weida W Xu Jinping J Gong Bo B Gao Beimin B Zhu Jiangfan J

Technology in cancer research & treatment 20200101

We previously showed that microRNA-182 (miR-182) might promote cell proliferation and migration in triple-negative breast cancer (TNBC). This study aimed to investigate circular RNAs (circRNAs) that interact with miR-182 and play important roles in TNBC. Thirty patients with TNBC were enrolled. One pair of tumor and adjacent tissue samples (control) were submitted for circRNA sequencing to establish the expression profile of circRNAs. Concomitantly, circRNAs aberrantly expressed between TNBC and ...[more]

PMID: 32938310

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Project description:IntroductionTriple-negative breast cancer (TNBC) is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs) presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs.Materials and methodsThe surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed.ResultsPositive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P = 0.014). The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P = 0.003). Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS) in both lymph node positive (LN+) and negative (LN-) cases (both P<0.001). Similarly it was also associated with shorter overall survival (OS)(P = 0.003 in LN+ cases; P = 0.018 in LN- cases). In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P = 0.008). Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P = 0.002). However, neither CLDN4 nor CLDN7 expression was associated with survival.ConclusionIn TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor in this heterogeneous subtype of breast cancer.

Project description:BackgroundHypoxia is a characteristic of breast tumours indicating poor prognosis. Based on the assumption that those genes which are up-regulated under hypoxia in cell-lines are expected to be predictors of poor prognosis in clinical data, many signatures of poor prognosis were identified. However, it was observed that cell line data do not always concur with clinical data, and therefore conclusions from cell line analysis should be considered with caution. As many transcriptomic cell-line datasets from hypoxia related contexts are available, integrative approaches which investigate these datasets collectively, while not ignoring clinical data, are required.ResultsWe analyse sixteen heterogeneous breast cancer cell-line transcriptomic datasets in hypoxia-related conditions collectively by employing the unique capabilities of the method, UNCLES, which integrates clustering results from multiple datasets and can address questions that cannot be answered by existing methods. This has been demonstrated by comparison with the state-of-the-art iCluster method. From this collection of genome-wide datasets include 15,588 genes, UNCLES identified a relatively high number of genes (>1000 overall) which are consistently co-regulated over all of the datasets, and some of which are still poorly understood and represent new potential HIF targets, such as RSBN1 and KIAA0195. Two main, anti-correlated, clusters were identified; the first is enriched with MYC targets participating in growth and proliferation, while the other is enriched with HIF targets directly participating in the hypoxia response. Surprisingly, in six clinical datasets, some sub-clusters of growth genes are found consistently positively correlated with hypoxia response genes, unlike the observation in cell lines. Moreover, the ability to predict bad prognosis by a combined signature of one sub-cluster of growth genes and one sub-cluster of hypoxia-induced genes appears to be comparable and perhaps greater than that of known hypoxia signatures.ConclusionsWe present a clustering approach suitable to integrate data from diverse experimental set-ups. Its application to breast cancer cell line datasets reveals new hypoxia-regulated signatures of genes which behave differently when in vitro (cell-line) data is compared with in vivo (clinical) data, and are of a prognostic value comparable or exceeding the state-of-the-art hypoxia signatures.

Project description:Background:Recently, long non-coding RNAs (lncRNAs) are important populations of non-coding RNAs with defined key roles in normal breast development as well as breast tumorigenesis. Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis because of highly invasive and no specific drug treatment yet. Breast cancer stems cells (BCSCs) cause a high risk of invasion, metastasis and drug resistance for breast cancer patients. Methods:Two microarrays of BCSCs and no-BCSCs were isolated from mammosphere-3D-cultured MCF-7 cells, differentially expressed lncRNAs (DELs) were screened out by Gene Expression Omnibus (GEO). Gene ontology enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to analyze DELs features. Using the STRING database to analyze DELs interaction network module to further screen the hub lncRNAs related to tumor stemness and make functional annotations. The expressions of hub DELs were validated using data from The Cancer Genome Atlas database. In addition, the expression analysis and survival analysis were conducted using GEO was utilized to analyze DELs in TNBC using GEPIA database. Results:A total of 143 aberrantly expressed lncRNAs in BCSCs were identified, and 25 lncRNAs were downregulated and 118 lncRNAs were upregulated compared to non-BCSCs. Up- and downregulated top 3 lncRNAs were selected and verified by RT-PCR. Notably, GO enrichment analysis and KEGG pathway analysis indicated that RNA transport, spliceosome, oxidative phosphorylation, NOD-like receptor signaling pathway, PI3K-Akt signaling pathway, and metabolic pathways may serve important roles in BCSCs. Additionally, the function loss assay indicated that ZGRF1 positively upregulated phenotype and biological functions of BCSCs in vitro. Collectively, our work establishes the lncRNAs signature in BCSCs and these findings assess us with evidence to explore further functionalities of lncRNAs in BCSCs and provide a novel therapeutic strategy for breast cancer. Conclusion:Our work establishes the lncRNAs signature in BCSCs and these findings assess us with evidence to explore further functionalities of lncRNAs in BCSCs and provide a novel therapeutic strategy for breast cancer. ZGRF1 expression is upregulated in TNBC patients and has a poor prognosis, which can be promising biomarkers.

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CircUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis.

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circUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis.

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