STARD13-correlated ceRNA network inhibits EMT and metastasis of breast cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Li X
PROVIDER: S-EPMC5029620 | biostudies-literature | 2016 Apr
REPOSITORIES: biostudies-literature
Publications
STARD13-correlated ceRNA network inhibits EMT and metastasis of breast cancer.
Li Xiaoman X Zheng Lufeng L Zhang Feng F Hu Jinhang J Chou Jinjiang J Liu Yu Y Xing Yingying Y Xi Tao T
Oncotarget 20160401 17
Competing endogenous RNAs (ceRNAs) network has been correlated with the initiation and development of cancer. Here, we identify CDH5, HOXD1, and HOXD10 as putative STARD13 ceRNAs and they display concordant patterns with STARD13 in different metastatic potential breast cancer cell lines and tissues. Notably, 3'UTRs of these genes suppress breast cancer metastasis via inhibiting epithelial-mesenchymal transition (EMT) in vitro and in vivo, which are activated through the crosstalk between STARD13 ...[more]
Similar Datasets
Project description:BACKGROUND:Targeting cancer stem cells is critical for suppressing cancer progression and recurrence. Finding novel markers or related pathways could help eradicate or diagnose cancer in clinic. METHODS:By constructing STARD13-correlated ceRNA 3'UTR stable overexpression or knockdown breast cancer cells, we aimed to explore the effects of STARD13-correlated ceRNA network on breast cancer stemness in vitro and in vivo. Further RNA-sequencing was used to analyze transcriptome change in combination with functional studies on candidate signaling. Clinical samples obtained from The Cancer Genome Atlas data were used to validate the correlation between STARD13 and related pathways. Finally, in vitro and in vivo experiments were used to examine the effects of STARD13-correlated ceRNA network on chemotherapy sensitivity/resistance. RESULTS:Here, we revealed that this ceRNA network inhibited stemness of breast cancer. Mechanistically, we found that activation of STARD13-correlated ceRNA network was negatively correlated with YAP/TAZ activity in breast cancer. Specifically, this ceRNA network attenuated YAP/TAZ nuclear accumulation and transcriptional activity via collectively modulating Hippo and Rho-GTPase/F-actin signaling. Finally, we demonstrated that YAP/TAZ transcriptional activity regulated by this ceRNA network was involved in chemoresistance. CONCLUSIONS:Our results uncover a novel mechanism of YAP/TAZ activation in breast cancer and propose the possibility to drive STARD13-correlated ceRNA network to inhibit breast cancer stem cell traits.
| S-EPMC5977742 | biostudies-literature
Project description:BackgroundBreast cancer is a malignancy and lethal tumor in women. Metastasis of breast cancer is one of the causes of poor prognosis. Increasing evidences have suggested that the competing endogenous RNAs (ceRNAs) were associated with the metastasis of breast cancer. Nonetheless, potential roles of ceRNAs in regulating the metastasis of breast cancer remain unclear.MethodsThe RNA expression (3 levels) and follow-up data of breast cancer and noncancerous tissue samples were downloaded from the Cancer Genome Atlas (TCGA). Differentially expressed and metastasis associated RNAs were identified for functional analysis and constructing the metastasis associated ceRNA network by comprehensively bioinformatic analysis. The Kaplan-Meier (K-M) survival curve was utilized to screen the prognostic RNAs in metastasis associated ceRNA network. Moreover, we further identified the metastasis associated biomarkers with operating characteristic (ROC) curve. Ultimately, the data of Cancer Cell Line Encyclopedia (CCLE, https://portals.broadinstitute.org/ccle) website were selected to obtained the reliable metastasis associated biomarkers.Results1005 mRNAs, 22 miRNAs and 164 lncRNAs were screened as differentially expressed and metastasis associated RNAs. The results of GO function and KEGG pathway enrichment analysis showed that these RNAs are mainly associated with the metabolic processes and stress responses. Next, a metastasis associated ceRNA (including 104 mRNAs, 19 miRNAs, and 16 lncRNAs) network was established, and 12 RNAs were found to be related to the overall survival (OS) of patients. In addition, 3 RNAs (hsa-miR-105-5p, BCAR1, and PANX2) were identified to serve as reliable metastasis associated biomarkers. Eventually, the results of mechanism analysis suggested that BCAR1 might promote the metastasis of breast cancer by facilitating Rap 1 signaling pathway.ConclusionIn the present research, we identified 3 RNAs (hsa-miR-105-5p, BCAR1 and PANX2) might associated with prognosis and metastasis of breast cancer, which might be provide a new perspective for metastasis of breast cancer and contributed to the treatment of breast cancer.
| S-EPMC8158160 | biostudies-literature
Project description:miRNA regulate gene expression at post-transcriptional level and fine-tune the key biological processes, including cancer progression. Here, we demonstrate the involvement of miR-200 b in the metastatic spread of prostate cancer. We identified miR-200 b as a downstream target of androgen receptor and linked its expression to decreased tumorigenicity and metastatic capacity of the prostate cancer cells. Overexpression of miR-200 b in PC-3 cells significantly inhibited their proliferation and the formation of subcutaneous tumors. Moreover, in an orthotopic model, miR-200 b blocked spontaneous metastasis and angiogenesis by PC-3 cells. This decreased metastatic potential was likely due to the reversal of the epithelial-to-mesenchymal transition, as was evidenced by increased pan-epithelial marker E-cadherin and specific markers of prostate epithelium, cytokeratins 8 and 18. In contrast, mesenchymal markers, fibronectin and vimentin, were significantly downregulated by miR-200 b. Our results suggest an important role for miR-200 b in prostate cancer progression and indicate its potential utility for prostate cancer therapy.
| S-EPMC3877136 | biostudies-literature
Project description:Tumor metastasis is the leading cause of death among breast cancer patients. PELP1 (proline, glutamic acid and leucine rich protein 1) is a nuclear receptor coregulator that is upregulated during breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer patients. Here, we show that PELP1 modulates expression of metastasis-influencing microRNAs (miRs) to promote cancer metastasis. Whole genome miR array analysis using PELP1-overexpressing and PELP1-underexpressing model cells revealed that miR-200 and miR-141 levels inversely correlated with PELP1 expression. Consistent with this, PELP1 knockdown resulted in lower expression of miR-200a target genes ZEB1 and ZEB2. PELP1 knockdown significantly reduced tumor growth and metastasis compared with parental cells in an orthotopic xenograft tumor model. Furthermore, re-introduction of miR-200a and miR-141 mimetics into PELP1-overexpressing cells reversed PELP1 target gene expression, decreased PELP1-driven migration/invasion in vitro and significantly reduced in vivo metastatic potential in a preclinical model of experimental metastasis. Our results demonstrated that PELP1 binds to miR-200a and miR-141 promoters and regulates their expression by recruiting chromatin modifier histone deacetylase 2 (HDAC2) as revealed by chromatin immunoprecipitation, small interfering RNA and HDAC inhibitor assays. Taken together, our results suggest that PELP1 regulates tumor metastasis by controlling the expression and functions of the tumor metastasis suppressors miR-200a and miR-141.
| S-EPMC3935988 | biostudies-literature
Project description:Honokiol (HNK), an active compound isolated from traditional Chinese medicine Magnolia officinalis, has shown potent anticancer activities. In the present study, we investigated the effects of HNK on breast cancer metastasis in vitro and in vivo, as well as the underlying molecular mechanisms. We showed that HNK (10-70 μmol/L) dose-dependently inhibited the viability of human mammary epithelial tumor cell lines MCF7, MDA-MB-231, and mouse mammary tumor cell line 4T1. In the transwell and scratch migration assays, HNK (10, 20, 30 μmol/L) dose-dependently suppressed the invasion and migration of the breast cancer cells. We demonstrated that HNK (10-50 μmol/L) dose-dependently upregulated the epithelial marker E-cadherin and downregulated the mesenchymal markers such as Snail, Slug, and vimentin at the protein level in breast cancer cells. Using a puromycin incorporation assay, we showed that HNK decreased the Snail translation efficiency in the breast cancer cells. In a mouse model of tumor metastasis, administration of HNK (50 mg/kg every day, intraperitoneal (i.p.), 6 times per week for 30 days) significantly decreased the number of metastatic 4T1 cell-derived nodules and ameliorated the histological alterations in the lungs. In addition, HNK-treated mice showed decreased Snail expression and increased E-cadherin expression in metastatic nodules. In conclusion, HNK inhibits EMT in the breast cancer cells by downregulating Snail and Slug protein expression at the mRNA translation level. HNK has potential as an integrative medicine for combating breast cancer by targeting EMT.
| S-EPMC6786377 | biostudies-literature
Project description:Background: Tamoxifen (TMX) is one of the most widely used drugs to treat breast cancer (BC). However, acquired drug resistance is still a major obstacle to its application, rendering it crucial to explore the mechanisms of TMX resistance in BC. This aims of this study were to identify the mechanisms of TMX resistance and construct ceRNA regulatory networks in breast cancer. Methods: GEO2R was used to screen for differentially expressed mRNAs (DEmRNAs) leading to drug resistance in BC cells. MiRTarbase and miRNet were used to predict miRNAs and lncRNAs upstream, and the competing endogenous RNA (ceRNA) regulatory network of BC cell resistance was constructed by starBase. We used the Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) to analyze the expression and prognostic differences of genes in the ceRNA network with core axis, and qRT-PCR was used to further verify the above conclusions. Results: We found that 21 DEmRNAs were upregulated and 43 DEmRNA downregulated in drug-resistant BC cells. DEmRNAs were noticeably enriched in pathways relevant to cancer. We then constructed a protein-protein interaction (PPI) network based on the STRING database and defined 10 top-ranked hub genes among the upregulated and downregulated DEmRNAs. The 20 DEmRNAs were predicted to obtain 113 upstream miRNAs and 501 lncRNAs. Among them, 7 mRNAs, 22 lncRNAs, and 11 miRNAs were used to structure the ceRNA regulatory network of drug resistance in BC cells. 4 mRNAs, 4 lncRNAs, and 3 miRNAs were detected by GEPIA and the Kaplan-Meier plotter to be significantly associated with BC expression and prognosis. The differential expression of the genes in BC cells was confirmed by qRT-PCR. Conclusion: The ceRNA regulatory network of TMX-resistant BC was successfully constructed and confirmed. This will provide an important resource for finding therapeutic targets for TMX resistance, where the discovery of candidate conventional mechanisms can aid clinical decision-making. In addition, this resource will help discover the mechanisms behind this type of resistance.
| S-EPMC9733938 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) is more aggressive and has poorer prognosis compared to other subtypes of breast cancer. Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal-like cells capable of migration, invasion, and metastasis. Recently, we have demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor and a lipid-lowering drug, could inhibit stemness properties of cancer stem cells (CSCs) derived from TNBC cell in vitro and in vivo. This study is aimed at investigating whether lovastatin inhibits TNBC CSCs by inhibiting EMT and suppressing metastasis and the mechanism involved. In the present study, we found that lovastatin dysregulated lysine succinylation of cytoskeleton-associated proteins in CSCs derived from TNBC MDA-MB-231 cell. Lovastatin inhibited EMT as demonstrated by down-regulation of the protein levels of Vimentin and Twist in MDA-MB-231 CSCs in vitro and vivo and by reversal of TGF-β1-induced morphological change in MCF10A cells. Lovastatin also inhibited the migration of MDA-MB-231 CSCs. The disruption of cytoskeleton in TNBC CSCs by lovastatin was demonstrated by the reduction of the number of pseudopodia and the relocation of F-actin cytoskeleton. Combination of lovastatin with doxorubicin synergistically inhibited liver metastasis of MDA-MB-231 CSCs. Bioinformatics analysis revealed that higher expression levels of cytoskeleton-associated genes were characteristic of TNBC and predicted survival outcomes in breast cancer patients. These data suggested that lovastatin could inhibit the EMT and metastasis of TNBC CSCs in vitro and in vivo through dysregulation of cytoskeleton-associated proteins.
| S-EPMC8212055 | biostudies-literature
Project description:BackgroundBreast cancer is the most common malignancy and has been considered as a leading cause of cancer death in women. Exploring the mechanism of breast cancer metastasis is extremely important for seeking novel therapeutic strategies and improving prognosis.MethodsClinical specimens and pathological characteristics were collected for evaluating the expression of forkhead box class O 3a (FOXO3a) and twist-related protein 1 (TWIST-1) in breast cancer tissues. CCK-8 assay was used to analyze cell proliferation. Cell invasion and migration were assessed by transwell assays. The expression of FOXO3a, TWIST-1, miR-10b, CADM2, FAK, phosphor-AKT and the epithelial-mesenchymal transition (EMT)-related protein (N-cadherin, E-cadherin and vimentin) were analyzed by RT-qPCR, immunohistochemical staining, immunofluorescence assay or western blot, respectively. Xenograft mouse models were used to analyze the role of the FOXO3a in breast cancer.ResultsFOXO3a was down-regulated and TWIST-1 was up-regulated in breast cancer tissues. Overexpression of FOXO3a or knockdown of TWIST-1 suppressed the proliferation, invasion, migration and EMT of breast cancer cells. Overexpression of TWIST-1 could reverse the effect of FOXO3a on the proliferation, invasion, migration and EMT of breast cancer. Moreover, FOXO3a suppressed the growth and metastasis of breast cancer by targeting TWIST1 in vivo.ConclusionFOXO3a inhibited the EMT and metastasis of breast cancer via TWIST-1/miR-10b/CADM2 axis.
| S-EPMC8081990 | biostudies-literature
Project description:Both epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are linked to metastasis via their ability to increase invasiveness and enhance tumor-initiating capacity. Growth factors, cytokines, and chemotherapies present in the tumor microenvironment (TME) are capable of inducing EMT, but the role of the extracellular matrix (ECM) in this process remains poorly understood. Here, a novel tessellated three-dimensional (3D) polymer scaffolding is used to produce a fibrillar fibronectin matrix that induces an EMT-like event that includes phosphorylation of STAT3 and requires expression of ?1 integrin. Consistent with these findings, analysis of the METABRIC dataset strongly links high-level fibronectin (FN) expression to decreased patient survival. In contrast, in vitro analysis of the MCF-10A progression series indicated that intracellular FN expression was associated with nonmetastatic cells. Therefore, differential bioluminescent imaging was used to track the metastasis of isogenic epithelial and mesenchymal cells within heterogeneous tumors. Interestingly, mesenchymal tumor cells do not produce a FN matrix and cannot complete the metastatic process, even when grown within a tumor containing epithelial cells. However, mesenchymal tumor cells form FN-containing cellular fibrils capable of supporting the growth and migration of metastatic-competent tumor cells. Importantly, depletion of FN allows mesenchymal tumor cells to regain epithelial characteristics and initiate in vivo tumor growth within a metastatic microenvironment.Implications: In contrast to the tumor-promoting functions of fibronectin within the ECM, these data suggest that autocrine fibronectin production inhibits the metastatic potential of mesenchymal tumor cells. Mol Cancer Res; 16(10); 1579-89. ©2018 AACR.
| S-EPMC6511995 | biostudies-literature
Project description:Breast cancer is the most frequently diagnosed malignancy among women, and triple-negative breast cancer (TNBC) is a highly aggressive subtype. Increasing evidence has shown that lncRNAs are involved in tumor growth, cell-cycle, and apoptosis through interactions with miRNAs or mRNAs. However, there is still limited data on ceRNAs involved in the molecular mechanisms underlying TNBC. In this study, we applied the weighted gene co-expression network analysis to the existing microarray mRNA and lncRNA expression data obtained from the breast tissues of TNBC patients to find the hub genes and lncRNAs involved in TNBC. Functional enrichment was performed on the module that correlated with Ki-67 status the most (Turquoise module). The hub genes in the Turquoise module were found to be associated with DNA repair, cell proliferation, and the p53 signaling pathway. We performed co-expression analysis of the protein-coding and lncRNA hub genes in the Turquoise module. Analysis of the RNA-seq data obtained from The Cancer Genome Atlas database revealed that the protein-coding genes and lncRNAs that were co-expressed were also differentially expressed in the TNBC tissues compared with the normal mammary tissues. On the basis of establishing the ceRNA network, two mRNAs (RAD51AP1 and TYMS) were found to be correlated with overall survival in TNBC. These results suggest that TNBC-specific mRNA and lncRNAs may participate in a complex ceRNA network, which represents a potential therapeutic target for the treatment of TNBC.
| S-EPMC6805880 | biostudies-other