Dataset Information

Expression and potential molecular mechanisms of miR?204?5p in breast cancer, based on bioinformatics and a meta?analysis of 2,306 cases.

ABSTRACT: Breast cancer (BC) is the most common cancer among women worldwide. However, there is insufficient research that focuses on the expression and molecular mechanisms of microRNA (miR)?204?5p in BC. In the current study, data were downloaded from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena databases. They were then used to undertake a meta?analysis that leveraged the standard mean difference (SMD) and summarized receiver operating characteristic (sROC) to evaluate the expression of the precursor miR?204 and mature miR?204?5p in BC. Additionally, an intersection of predicted genes, differentially expressed genes (DEGs) from the TCGA database and the GEO database were plotted to acquire desirable putative genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein?protein interaction (PPI) network analyses were performed to assess the potential pathways and hub genes of miR?204?5p in BC. A decreased trend in precursor miR?204 expression was detected in 1,077 BC tissue samples in comparison to 104 para?carcinoma tissue samples in the TCGA database. Further, the expression of mature miR?204?5p was markedly downregulated in 756 BC tissue samples in comparison to 76 para?carcinoma tissue samples in the UCSC Xena database. The outcome of the SMD from meta?analysis also indicated that the expression of miR?204?5p was markedly reduced in 2,306 BC tissue samples in comparison to 367 para?carcinoma tissue samples. Additionally, the ROC and sROC values indicated that miR?204?5p had a great discriminatory capacity for BC. In GO analysis, 'cell development', 'cell surface activity', and 'receptor agonist activity' were the most enriched terms; in KEGG analysis, 'endocytosis' was significantly enriched. Rac GTPase activating protein 1 (RACGAP1) was considered the hub gene in the PPI network. In conclusion, miR?204?5p may serve a suppressor role in the oncogenesis and advancement of BC, and miR?204?5p may have crucial functions in BC by targeting RACGAP1.

SUBMITTER: Cai KT

PROVIDER: S-EPMC6323248 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression and potential molecular mechanisms of miR‑204‑5p in breast cancer, based on bioinformatics and a meta‑analysis of 2,306 cases.

Cai Kai-Teng KT Liu An-Gui AG Wang Ze-Feng ZF Jiang Hang-Wei HW Zeng Jing-Jing JJ He Rong-Quan RQ Ma Jie J Chen Gang G Zhong Jin-Cai JC

Molecular medicine reports 20181214 2

Breast cancer (BC) is the most common cancer among women worldwide. However, there is insufficient research that focuses on the expression and molecular mechanisms of microRNA (miR)‑204‑5p in BC. In the current study, data were downloaded from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena databases. They were then used to undertake a meta‑analysis that leveraged the standard mean difference (SMD) and summarized receiver ...[more]

PMID: 30569120

Similar Datasets

Project description:BackgroundCircular RNA RHOT1 (circRHOT1) plays crucial roles in tumorigenesis by competing with microRNAs. It is largely abundant in tumor cell-derived exosomes. Meanwhile, cancer-derived exosomes participate in diverse biological processes. However, the expression patterns and functions of exosomal circRHOT1 in breast cancer remain unknown. This study is aimed to investigate and elucidate the exosomal circRHOT1/miR-204-5p/PRMT5 axis in breast cancer.MethodsThe exosomes derived from serum samples of breast cancer patients and breast cancer cell lines were characterized using transmission electron microscopy and Western blot. MTT, colony formation, wound healing, and transwell assays were utilized to analyze cell proliferation, migration, and invasion of breast cancer cells. Flow cytometry was used for apoptosis analysis. The bioinformatics method was employed to screen differentially expressed novel circRNAs and predict the microRNA targets of circRHOT1. Dual-luciferase reporter gene assays were performed to verify their direct interaction. Finally, Xenograft experiments were used to investigate the effect of exosomal circRHOT1 on tumor growth in vivo.ResultsCircRHOT1 exhibited significantly high expression in exosomes derived from the serum of breast cancer patients and breast cancer cell lines, which suggested its potential diagnostic value. Breast cancer-derived exosomes promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells while inhibiting apoptosis. However, exosomes with downregulated circRHOT1 inhibited the growth of co-cultured cells. Mechanistically, circRHOT1 acted as a sponge of miR-204-5p and promoted protein arginine methyltransferase 5 (PRMT5) expression. Moreover, miR-204-5p inhibitor and pcPRMT5 could reverse the tumor suppressive effects mediated by circRHOT1-knockdown. Furthermore, treatment with exosomes derived from breast cancer cells with circRHOT1 knockdown attenuated tumor growth in tumor-bearing nude mice, which was accompanied by a reduction in PRMT5 expression and an enhancement of miR-204-5p expression.ConclusionThe exosomal circRHOT1 may promote breast cancer progression by regulating the miR-204-5p/PRMT5 axis. The current study strengthens the role of circRHOT1, miR-204-5p, and PRMT5 in breast cancer development and provides a potential treatment strategy for breast cancer.

Project description:Breast cancer (BC) has been identified as the leading malignancy in women worldwide. However, the potential molecular mechanism of microRNA (miR)‑203a‑3p in BC remains to be elucidated. The present study evaluated the expression of miR‑203a‑3p in BC and adjacent normal tissue in several publically available datasets. The distinguishability of precursor miR‑203a and miR‑203a‑3p in BC tissue and adjacent breast tissue was assessed using receiver operating characteristic (ROC) and summarized ROC (sROC) approaches. In addition, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes pathway analysis and protein‑protein interaction analysis were performed to determine the potential molecular mechanism of miR‑203a‑3p in BC. It was identified that the expression of precursor miR‑203a was markedly upregulated in 1,077 BC tissue samples compared to 104 adjacent breast tissue samples from The Cancer Genome Atlas. Additionally, an increasing trend in miR‑203a‑3p expression was observed in 756 BC tissue samples compared with 76 adjacent breast tissue samples from the University of California Santa Cruz Xena project. In addition, a comprehensive meta‑analysis suggested that the expression of miR‑203a‑3p was markedly increased in 2,444 BC tissue samples compared with 559 adjacent breast tissue samples. The area under the curve of the ROC and sROC revealed that miR‑203a‑3p expression was able to distinguish between BC tissue and adjacent breast tissue. However, miR‑203a‑3p exhibited no prognostic value in BC. The results of GO enrichment demonstrated that the miR‑203a target genes were associated with 'plasma membrane integrity', 'cell surface receptor linked signal and transduction' and '3',5'‑cyclic nucleotide phosphodiesterase activity'. 'Purine metabolism' was identified as the pathway with the most enrichment of miR‑203a‑3p target genes in BC. The present study also identified insulin‑like growth factor receptor (IGF1) as a hub gene associated with miR‑203a in BC. In summary, miR‑203a‑3p may enhance the development and oncogenesis of BC, and IGF1 was defined as a hub gene of miR‑203a‑3p in BC.

Project description:Lung cancer is a leading cause of mortality worldwide and despite recent improvements in lung cancer treatments patient mortality remains high. miR-193a-5p serves a crucial role in the initiation and development of cancer; it is necessary to understand the underlying molecular mechanisms of miR-193a-5p in lung cancer, which may enable the development of improved clinical diagnoses and therapies. The present study investigated the diagnostic value of peripheral blood and tissue miR-193a-5p expression using a microarray meta-analysis. Peripheral blood miR-193a-5p was revealed to be upregulated in patients with lung cancer. The pooled area under the curve (AUC) was 0.67, with a sensitivity and specificity of 0.74 and 0.56, respectively. Conversely, the peripheral tissue miR-193a-5p expression in patients with lung cancer was significantly downregulated. The pooled AUC was 0.83, and the sensitivity and specificity were 0.65 and 0.89, respectively. Through bioinformatics analysis, three Kyoto Encyclopedia of Genes and Genomes (KEGG) terms, pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway, were identified as associated with miR-193a-5p in lung cancer. In addition, in lung cancer, six key miR-193a-5p target genes, receptor tyrosine-protein kinase erbB-2 (ERBB2), nuclear cap-binding protein subunit 2 (NCBP2), collagen ?-1(I) chain (COL1A1), roprotein convertase subtilisin/kexin type 9 (PCSK9), casein kinase II subunit ? (CSNK2A1) and nucleolar transcription factor 1 (UBTF), were identified, five of which were significantly upregulated (ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF). The protein expression of ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF was also upregulated. NCBP2 and CSNK2A1 were negatively correlated with miR-193a-5p. The results demonstrated that miR-193a-5p exhibited opposite expression patterns in peripheral blood and tissue. Upregulated peripheral blood miR-193a-5p and downregulated tissue miR-193a-5p may be promising diagnostic biomarkers in lung cancer. In addition, the KEGG terms pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway may suggest which pathways serve vital roles in lung cancer by regulating miR-193a-5p. In addition, six genes, ERBB2, COL1A1, PCSK9, UBTF and particularly NCBP2 and CSNK2A1, may be key target genes of miR-193a-5p in lung cancer.

Dataset Information

Expression and potential molecular mechanisms of miR?204?5p in breast cancer, based on bioinformatics and a meta?analysis of 2,306 cases.

Publications

Expression and potential molecular mechanisms of miR‑204‑5p in breast cancer, based on bioinformatics and a meta‑analysis of 2,306 cases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets