A functional link between miR-200a and ELK3 regulates the metastatic nature of breast cancer
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ABSTRACT:
PROVIDER: PRJNA625036 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11539654.fastq.gz | Fastqsanger.gz | |||
| SRR11539655.fastq.gz | Fastqsanger.gz | |||
| SRR11539656.fastq.gz | Fastqsanger.gz | |||
| SRR11539657.fastq.gz | Fastqsanger.gz | |||
| SRR11539658.fastq.gz | Fastqsanger.gz |
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Project description:The ectopic expression of miR-200a impaired the migration and invasion of TNBC cells by reducing the expression level of the ELK3 mRNA. An analysis of differentially expressed genes showed that the control group - and miR-200a plus ELK3 group had similar genetic signatures that differed from that of the miR-200a alone group.
2020-04-14 | GSE148562 | GEO
Project description:Triple-negative breast cancer (TNBC) refers to breast cancer that does not have receptors for estrogen, progesterone, and HER2 protein. TNBC accounts for 10-20% of all cases of breast cancers and is characterized by its metastatic aggressiveness, poor prognosis, and limited treatment options. Here, we show that the metastatic nature of TNBC is critically regulated by a functional link between miR-200a and the transcription factor ELK3. We found that the expression levels of miR-200a and the ELK3 mRNA were negatively correlated in the luminal and TNBC subtypes of breast cancer cells. In vitro experiments revealed that miR-200a directly targets the 3' untranslated region (UTR) of the ELK3 mRNA to destabilize the transcripts. Furthermore, ectopic expression of miR-200a impaired the migration and invasion of TNBC cells by reducing the expression level of the ELK3 mRNA. In in vivo studies, transfection of MDA-MB 231 cells (a claudin-low TNBC cell type) with exogenous miR-200a reduced their extravasation into the lung during 48 h after tail vein injection, and co-transfection of the cells with an expression plasmid harboring ELK3 that lacked an intact 3'UTR recovered their extravasation ability. Overall, our findings provide evidences that miR-200a and ELK3 is functionally linked to regulate invasive characteristics of breast cancers.
| S-EPMC7281469 | biostudies-literature
Project description:Three metastatic melanoma cell lines (BD-0548-ME, DP-0574-ME and WP-0614-ME) were transfected with miR precursors: hsa-miR negative control (NC) or hsa-miR-200a-3p precursors (miR-200a). The objective of this experiment was to determine miR-200a targets in metastatic melanoma cell lines. We selected low -miR-200a expression cell lines and then we overexpressed miR-200a or NC. Finally, we compared the metastatic melanoma cell lines with miR-200a overexpression (miR-200a) to the same cell line transfected with the negative control miR (NC).
2018-06-20 | GSE83512 | GEO
Project description:Current therapeutic strategies, including surgery and chemotherapy, for gastric cancer improve survival; however, the survival rate for those with metastatic gastric cancer is very low. The molecular mechanisms underlying dissemination of gastric cancer cells to distant organs are unknown. Here, we show that the ELK3 gene is necessary for migration and invasion of gastric cancer cells. The ELK3 gene modulates expression of extracellular matrix (ECM) remodeling-related genes such as LOXL2, SERPINF1, COL16A1, NID1, and SNAI1 to facilitate cancer cell dissemination. Our in silico analysis indicated that ELK3 expression was positively correlated with these ECM remodeling-related genes in gastric cancer cells and human gastric cancer patients. High expression of ELK3 and other ECM remodeling-related genes was also closely associated with a worse prognosis of gastric cancer patients. These findings suggested that ELK3 acts as an important regulator of gastric cancer dissemination by regulating ECM remodeling.
2021-09-14 | GSE181840 | GEO
Project description:Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 results in the extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated and we found that suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells. Retrovirus expressing shRNA of ELK3 was transduced into MDA-MB-231 cell line and stable cell line of which ELK3 is suppressed more than 50% was selected by the drug selection (Puromycin).
2016-06-15 | E-GEOD-83325 | biostudies-arrayexpress
Project description:The molecular response to hypoxia is a critical cellular process implicated in cancer, and a target for drug development. The activity of the major player, HIF1M-NM-1,M-BM- is regulated at different levels, including the transcriptional level by the Ets factor ELK3. The molecular mechanisms of this intimate transcriptional connection remain largely unknown. Whilst investigating global ELK3-chromatin interactions, we uncovered an unexpected connection that involves the microRNA hsa-miR-155-5p, a hypoxia-inducible oncomir that targets HIF1M-NM-1. One of the ELK3 chromatin binding sites, detected by Chromatin Immuno-Precipitation Sequencing (ChIP-seq) of normal Human Umbilical Vein Endothelial Cells (HUVEC), is located at the transcription start site of the MIR155HG genes that expresses hsa-miR-155-5p. We confirmed that ELK3 binds to this promoter by ChIP and QPCR. We showed that ELK3 and hsa-miR-155-5p form a double-negative regulatory loop. ELK3 depletion induced hsa-miR-155-5p expression, and hsa-miR-155-5p expression decreased ELK3 expression at the RNA level through a conserved target sequence in its 3M-bM-^@M-^Y-UTR. We further showed that the activities of hsa-miR-155-5p and ELK3 are functionally linked. Pathway analysis indicates that both factors are implicated in related processes, including cancer and angiogenesis. hsa-miR-155-5p expression and ELK3 depletion have similar effects on expression of known ELK3 target genes, and in-vitro angiogenesis and wound closure. Bioinformatic analysis of cancer RNA-seq data shows that hsa-miR-155-5p and ELK3 expression are significantly anti-correlated, as would be expected from hsa-miR-155-5p targeting ELK3 RNA. Hypoxia (0% oxygen) down-regulates ELK3 mRNA in a microRNA and hsa-miR-155-5p dependent manner. These results tie ELK3 into the hypoxia response pathway through an oncogenic microRNA and into a circuit implicated in the dynamics of the hypoxic response.M-BM- This crosstalk could be important in the development of new treatments for a range of pathologies. Examination of ELK3 DNA interactions in HUVEC cells under normal oxygen conditions
2014-12-04 | E-GEOD-60156 | biostudies-arrayexpress
Project description:Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 results in the extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated and we found that suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells.
2016-06-15 | GSE83325 | GEO
Project description:To further development of the effects of miR-200a in ovarian cancer OVCAR3 cells，we have employed lncRNA and mRNA microarray as a discovery platform to identify lncRNA and mRNA expression in miR-200a overexpressing ovarian cancer cells. OVCAR3 cells were transfected with lentiviral vector with eGFP, encoding miR-200a and negative control vector (LV- miR-200a and LV-CON,) by using polybrene. The dysregulation of miR-200a was confirmed by using RT-PCR. RNA was extracted and detected by a lncRNA and mRNA microarray in LV-miR-200a and LV-CON OVCAR3 cells. The different expression of lncRNA and mRNA in LV-miR-200a and LV-CON OVCAR3 cells was analyzed to explore the mechanism that miR-200a affect ovarain cancer cells.
2018-11-04 | GSE122123 | GEO
Project description:Background Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer because of its aggressive behavior and the limited therapeutic strategies available. In the last decade, immunotherapy has become a promising treatment to prolong survival in advanced solid cancers including TNBC. However, the efficacy of immunotherapy in solid cancers remains limited because solid tumors contain few tumor-infiltrating lymphocytes. Methods A proteome profiler array was performed to identify secreted CXCL16 protein, the expression of which is regulated by ELK3 to control natural killer (NK) cell-mediated cytotoxicity. The correlation between ELK3 and CXCL16 was investigated by microarray and TCGA data analysis. NK cell cytotoxicity and migration assays were performed to examine the role of ELK3-CXCL16 in regulating the anticancer effect in TNBC. CXCL16-mediated NK cell recruitment and NK cell cytotoxicity were examined in an experimental metastasis mouse model and in an MDA-MB231 orthotopic mouse model. Results We show that targeting the ETS transcription factor ELK3 recruits immune cells including NK cells into tumors via the chemotactic activity of the chemokine. ELK3 depletion upregulated CXCL16 expression, thereby inducing NK cell recruitment to tumors and increasing NK cell cytotoxicity in TNBC . In silico analysis showed that ELK3 is negatively correlated with CXCL16 expression in breast cancer patient samples. Low expression of ELK3 and high expression of CXCL16 were associated with a better prognosis. Low expression of ELK3 and high expression of CXCL16 were associated with increased expression of NK cell-related genes. Conclusions The ELK3-CXCL16 axis regulates NK cell recruitment and increases NK cell cytotoxicity, suggesting that targeting the ELK3 gene could be an adjuvant strategy for increasing the efficacy of immunotherapy in TNBC.
2022-07-20 | GSE208584 | GEO
Project description:The miR-200 family of microRNAs consisting of miR-141, miR-200a, miR-200b, miR-200c and miR-429 are key regulators of breast cancer progression. The miR200 family maintains mammary epithelial identity and downregulation of miR-200 expression drives the epithelial-to-mesenchymal transition. Re-expression of one or more miR-200 family members in tumor cells with mesenchymal characteristics may restore the epithelial phenotype and alter growth and metastatic potential. To test this, the miR-200b/200a/429 cluster was re-expressed in a murine claudin-low mammary tumor cell line, RJ423
2018-10-31 | GSE113162 | GEO