CDYL2 epigenetically regulates MIR124 to control NF-kB/STAT3-dependent breast cancer cell plasticity [MDA-MB-231 RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA631763 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11772883_1.fastq.gz | Fastqsanger.gz | |||
| SRR11772883_2.fastq.gz | Fastqsanger.gz | |||
| SRR11772884_1.fastq.gz | Fastqsanger.gz | |||
| SRR11772884_2.fastq.gz | Fastqsanger.gz | |||
| SRR11772885_1.fastq.gz | Fastqsanger.gz |
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Project description:Epigenetic deregulation of gene transcription is central to cancer cell plasticity and malignant progression, but remains poorly understood. We found that the uncharacterized epigenetic factor Chromodomain on Y-like 2 (CDYL2) is commonly over-expressed in breast cancer, and that high CDYL2 levels correlate with poor prognosis. Supporting a functional role for CDYL2 in malignancy, it positively regulated breast cancer cell migration, invasion, stem-like phenotypes, and epithelial-to-mesenchymal transition (EMT). CDYL2 regulation of these plasticity-associated processes depended on signaling via p65/NF-kB and STAT3. This, in turn, was downstream of CDYL2 regulation of MIR124 gene transcription. CDYL2 co-immunoprecipitated with G9a/EHMT2 and GLP/EHMT1, and regulated the chromatin enrichment of G9a and EZH2 at MIR124 genes. We propose that CDYL2 contributes to poor prognosis in breast cancer by recruiting G9a and EZH2 to epigenetically repress MIR124 genes, thereby promoting NF-kB and STAT3 signaling, as well as downstream cancer cell plasticity and malignant progression.
2020-05-17 | GSE150319 | GEO
Project description:Epigenetic deregulation of gene transcription is central to cancer cell plasticity and malignant progression, but remains poorly understood. We found that the uncharacterized epigenetic factor Chromodomain on Y-like 2 (CDYL2) is commonly over-expressed in breast cancer, and that high CDYL2 levels correlate with poor prognosis. Supporting a functional role for CDYL2 in malignancy, it positively regulated breast cancer cell migration, invasion, stem-like phenotypes, and epithelial-to-mesenchymal transition (EMT). CDYL2 regulation of these plasticity-associated processes depended on signaling via p65/NF-kB and STAT3. This, in turn, was downstream of CDYL2 regulation of MIR124 gene transcription. CDYL2 co-immunoprecipitated with G9a/EHMT2 and GLP/EHMT1, and regulated the chromatin enrichment of G9a and EZH2 at MIR124 genes. We propose that CDYL2 contributes to poor prognosis in breast cancer by recruiting G9a and EZH2 to epigenetically repress MIR124 genes, thereby promoting NF-kB and STAT3 signaling, as well as downstream cancer cell plasticity and malignant progression.
2020-05-17 | GSE150306 | GEO
Project description:Epigenetic deregulation of gene transcription is central to cancer cell plasticity and malignant progression, but remains poorly understood. We found that the uncharacterized epigenetic factor Chromodomain on Y-like 2 (CDYL2) is commonly over-expressed in breast cancer, and that high CDYL2 levels correlate with poor prognosis. Supporting a functional role for CDYL2 in malignancy, it positively regulated breast cancer cell migration, invasion, stem-like phenotypes, and epithelial-to-mesenchymal transition (EMT). CDYL2 regulation of these plasticity-associated processes depended on signaling via p65/NF-kB and STAT3. This, in turn, was downstream of CDYL2 regulation of MIR124 gene transcription. CDYL2 co-immunoprecipitated with G9a/EHMT2 and GLP/EHMT1, and regulated the chromatin enrichment of G9a and EZH2 at MIR124 genes. We propose that CDYL2 contributes to poor prognosis in breast cancer by recruiting G9a and EZH2 to epigenetically repress MIR124 genes, thereby promoting NF-kB and STAT3 signaling, as well as downstream cancer cell plasticity and malignant progression.
2020-05-17 | GSE150274 | GEO
Project description:CDYL2 epigenetically regulates MIR124 to control NF-kB/STAT3-dependent breast cancer cell plasticity
| PRJNA631761 | ENA
Project description:CDYL2 epigenetically regulates MIR124 to control NF-kB/STAT3-dependent breast cancer cell plasticity [ChIP-seq]
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Project description:CDYL2 epigenetically regulates MIR124 to control NF-kB/STAT3-dependent breast cancer cell plasticity [RNA-seq]
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Project description:In the past decades, altered Follistatin‑like 1 (FSTL1) expression has been documented in a variety of cancers, while its functional roles are poorly understood. Particularly in breast cancer, the expression of FSTL1 and its signaling pathway remain to be determined. In the present study, an elevated FSTL1 expression and a supressed cell proliferation were detected in a specific brain metastatic cell line MDA‑MB‑231‑BR (231‑BR), compared with its parental cell line MDA‑MB‑231. However, this protein was hardly detected in the other three breast cancer cell lines. Next, lentiviral vectors encoding FSTL1 or FSTL1 specific shRNAs were used to overexpress or knock down FSTL1 in MDA‑MB‑231 or 231‑BR, respectively (MDA‑MB‑231FSTL1 or 231‑BRsh FSTL1). Results showed that overexpression of FSTL1 inhibited MDA‑MB‑231 cell proliferation, while knockdown of FSTL1 in 231‑BR cells promotes cell proliferation, compared with their corresponding control groups. These results were further confirmed in nude mouse xenografts. The tumor volume in 231‑BR cell-bearing mice was significantly smaller than that of MDA‑MB‑231 group, and reduction of tumor volume was detected in MDA‑MB‑231FSTL1 cell-bearing mice compared with the control group. Previous studies revealed that TGF‑β-Smad2/3 signaling pathway was activated in 231‑BR and MDA‑MB‑231FSTL1 cells, which may contribute to the inhibited cell proliferation. In addition, Smad3 knockdown could restore the inhibition of cell proliferation induced by FSTL1 overexpression in MDA‑MB‑231FSTL1 cells, indicating that the anti‑proliferative effect of FSTL1 overexpression may be associated with Smad3 involved TGF‑β signaling pathway regulation. This study identified FSTL1 as an inhibitor of cell proliferation in MDA‑MB‑231 and 231‑BR cell lines, which may provide new insights into the development and management of breast cancer.
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