Similar Datasets
Project description:PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. PAX2 promotes cell proliferation, oncogenic transformation, cell lineage specification, migration, and survival. In our previous study, we found that PAX2 is highly expressed in low-grade ovarian serous carcinoma, but its expression in clear cell, endometrioid, and mucinous cell ovarian carcinomas have not been studied. More importantly, the functional role of PAX2 in ovarian cancer is not known. Downregulation of PAX2 in PAX2-expressing ovarian cancer cells inhibits cell proliferation and migration. This growth inhibition is due to the upregulation of the tumor suppressor gene G0S2 and subsequent induction of apoptosis. The PAX2 pathway thus represents a potential therapeutic target for PAX2-expressing ovarian carcinomas. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, and gene expression profiles.
2011-12-05 | E-GEOD-30501 | biostudies-arrayexpress
Project description:PCa-LINES: Ribo-minus RNA-seq of 4 patient samples and 2 PCa cell lines
| EGAS00001004613 | EGA
Project description:PCa-LINES: rRNA-minus RNA-seq of PCa cell-lines (VCaP & PC346c) and 4 additional patient samples
| EGAD00001006366 | EGA
Project description:DNA-level alterations conferring selective cell growth advantages (mutations) are a well-established source of heritable variation underpinning cancer initiation and progression. Heritable changes in cell states not due to alterations in DNA sequence (epimutations) are also proposed to contribute to cancer, but concrete examples involving specific genes are elusive. Endometrial cancer is a common, lethal malignancy of women, understood to arise through the stepwise selection of heritable changes that result first in the formation of a preinvasive precursor known as endometrioid intraepithelial neoplasia, followed by progression to cancer. PAX2 is required for the embryological specification of endometrium, and PAX2 endometrial expression persists throughout life. Per clinical studies, loss of PAX2 protein occurs in 80% of endometrial cancers. However, the molecular basis of PAX2 loss—and its functional significance—remain unknown. Here, we show that loss of PAX2 protein occurs through a specific transcriptional gene silencing event (an epimutation) specifically targeting PAX2. This RNA-level silencing event occurs in early microscopic neoplastic clones preceding endometrioid intraepithelial neoplasia, linking PAX2 silencing with the initiation of most endometrial cancers. PAX2 silencing is associated with loss of a promoter-proximal active enhancer, and 3D genome organization studies of cell lines and patient-derived tumors showed that repressive H3K27me3 marks span an insulated gene neighborhood formed via a looping mechanism, restraining spread of the H3K27me3 domain. PAX2 broadly regulates enhancer activity and transcription in endometrial cancer cells including PGR, rationalizing its activity as an oncodevelopmental tumor suppressor. Functional studies, including of a novel mouse model and tumor-derived organoids based on endometrial-specific Pax2 inactivation, proved that Pax2 is a bona fide tumor suppressor in vivo that potently cooperates with Pten, the second most frequently inactivated tumor suppressor in endometrial cancer. PAX2 silencing was reversible in human cell lines, suggesting that PAX2 may be a druggable target. Taken together, our findings establish a new paradigm for cancer-driving epimutations and open new lines of investigation into the mechanistic basis of endometrial cancer, with diverse implications for its diagnosis and treatment.
2025-06-03 | GSE275320 | GEO
Project description:Withaferin A (WA) is a lactone extracted from Withania somnifera commonly known as Ashwagandha. WA has several therapeutic benefits. The current study was aimed to identify biomarkers that could be targeted by WA in prostate cancer (PCA) cells. We have used SILAC approach to identify WA-regulated proteins at 4 h and 24 time points in three PCA cell lines such as LNCaP, 22Rv1 and DU-145. Ontology prediction suggested that WA treatment can upregulate stress-responsive pathways and shutdown translation and cell metabolism to conserve energy. The cytoprotective stress granule (SG) protein G3BP1 showed upregulation in all the three tested cell lines in response to WA treatment, and subsequently, SGs formed at a higher rate in the WA treated cells. Knockdown (KD) of G3BP1 blocked WA-induced SG formation and reduced the cell survival. We speculate that the activation of G3BP1 and the formation of SGs might constitute a mechanism by which PCA cells induce cell protection after WA- treatment. Knock down of SG proteins such as G3BP1 could help to evade the cytoprotective effects of WA and to assist in the sensitization of cells.
2021-07-21 | PXD016759 | Pride
Project description:In this study, we knockdown the expression of CTCF in EL4 cells by shRNA, followed by single cell RNA-seq on both wild type (WT) cells and CTCF-Knockdown (CTCF-KD) cells. Principal component analysis (PCA) of single cell RNA-seq data showed that WT cells and CTCF-KD cells essentially concentrated in two different clusters on the PCA projection, indicating gene expression profiles of CTCF-KD cells and WT cells were systematically different. We further found the cells’ CTCF expression levels were correlated with the cell’s positioning on PCA projection. Interestingly, GO terms including regulation of transcription, DNA binding, Zinc finger and transcription factor binding are significantly enriched in CTCF-KD specific highly variable genes, indicating tissue specific genes such as transcription factors were highly sensitive to CTCF-KD level and showed strongly increased variation. While the housekeeping genes including rRNA processing, DNA repair and tRNA processing are significantly enriched in WT specific highly variable genes, potentially indicating cell-to-cell variation of cell activity in WT cells is higher than that of CTCF-KD cells. We found CTCF-KD cell specific highly variable genes were significantly enriched in CTCF-KD specific down-regulated genes, indicating knockdown of CTCF simultaneously reduced expression levels and increased gene expression noises of its target genes. In summary, analysis of genome-wide cell-to-cell variation in this study showed CTCF-medicated promoter-enhancer interaction not only important for maintaining the expression of its target genes, but also played important roles in reducing the expression noise of its target genes.
2020-01-08 | GSE135769 | GEO
Project description:We profiled the proteomics of prostate cancer (PCa) cell lines.
2024-12-06 | PXD058635 |
Project description:DNA-level alterations (mutations) conferring selective cell growth advantages are well-established in cancer initiation and progression. Changes in cell states not due to alterations in DNA sequence (epimutations) are also proposed to contribute to cancer, but concrete examples involving specific genes are elusive. Endometrial cancer is a common, lethal malignancy of women, understood to arise through the stepwise selection of heritable changes that result first in the formation of a preinvasive precursor known as endometrioid intraepithelial neoplasia, followed by progression to cancer. PAX2 is required for the development of endometrium in embryos, and PAX2 endometrial expression persists throughout life. Per clinical studies, loss of PAX2 protein occurs in 80% of endometrial cancers. However, the molecular basis of PAX2 loss—and its functional significance—remain unknown. Here, we show that loss of PAX2 protein occurs through a specific transcriptional gene silencing event specifically targeting PAX2. This RNA-level silencing event occurs in early microscopic neoplastic clones preceding endometrioid intraepithelial neoplasia, linking PAX2 silencing with the initiation of most endometrial cancers. Integrated genomic, transcriptomic, epigenomic, 3D genomic, and machine learning approaches showed that loss of PAX2 expression is associated with replacement of open/active chromatin features (H3K27ac and H3K4me3) with inaccessible chromatin features (H3K27me3). The spread of the H3K27me3 signal resembles a pearl necklace, with its length modulated by cohesin loops, preventing transcriptional dysregulation of neighboring genes, thereby limiting PAX2 silencing as a focal epigenetic event. PAX2 broadly regulates enhancer activity and transcription in endometrial cancer cells including PGR, rationalizing its activity as an oncodevelopmental tumor suppressor. Functional studies, including of a novel mouse model and tumor-derived organoids based on endometrial-specific Pax2 inactivation, proved that Pax2 is a bona fide tumor suppressor in vivo that potently cooperates with Pten, the second most frequently inactivated tumor suppressor in endometrial cancer. PAX2 silencing was reversible in human cell lines, suggesting that PAX2 may be a druggable target. Taken together, our findings establish a new paradigm for cancer-driving epimutations and open new lines of investigation into the origins of endometrial cancer, with diverse implications for its diagnosis and treatment.
2025-06-03 | GSE275310 | GEO
Project description:DNA-level alterations (mutations) conferring selective cell growth advantages are well-established in cancer initiation and progression. Changes in cell states not due to alterations in DNA sequence (epimutations) are also proposed to contribute to cancer, but concrete examples involving specific genes are elusive. Endometrial cancer is a common, lethal malignancy of women, understood to arise through the stepwise selection of heritable changes that result first in the formation of a preinvasive precursor known as endometrioid intraepithelial neoplasia, followed by progression to cancer. PAX2 is required for the development of endometrium in embryos, and PAX2 endometrial expression persists throughout life. Per clinical studies, loss of PAX2 protein occurs in 80% of endometrial cancers. However, the molecular basis of PAX2 loss—and its functional significance—remain unknown. Here, we show that loss of PAX2 protein occurs through a specific transcriptional gene silencing event specifically targeting PAX2. This RNA-level silencing event occurs in early microscopic neoplastic clones preceding endometrioid intraepithelial neoplasia, linking PAX2 silencing with the initiation of most endometrial cancers. Integrated genomic, transcriptomic, epigenomic, 3D genomic, and machine learning approaches showed that loss of PAX2 expression is associated with replacement of open/active chromatin features (H3K27ac and H3K4me3) with inaccessible chromatin features (H3K27me3). The spread of the H3K27me3 signal resembles a pearl necklace, with its length modulated by cohesin loops, preventing transcriptional dysregulation of neighboring genes, thereby limiting PAX2 silencing as a focal epigenetic event. PAX2 broadly regulates enhancer activity and transcription in endometrial cancer cells including PGR, rationalizing its activity as an oncodevelopmental tumor suppressor. Functional studies, including of a novel mouse model and tumor-derived organoids based on endometrial-specific Pax2 inactivation, proved that Pax2 is a bona fide tumor suppressor in vivo that potently cooperates with Pten, the second most frequently inactivated tumor suppressor in endometrial cancer. PAX2 silencing was reversible in human cell lines, suggesting that PAX2 may be a druggable target. Taken together, our findings establish a new paradigm for cancer-driving epimutations and open new lines of investigation into the origins of endometrial cancer, with diverse implications for its diagnosis and treatment.
2025-06-03 | GSE275309 | GEO