RNA sequencing of human breast cancer cells with CUL4B knockdown
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE158651 | GEO | 2022/09/08
REPOSITORIES: GEO
Similar Datasets
Project description:Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, has been reported to be overexpressed in several types of solid tumors and contributes to epigenetic silencing of tumor suppressor. However, its clinical significance and the molecular mechanisms underlying its regulation in gastric cancer (GC) remain largely unknown. Here, we showed that CUL4B was elevated in GC tissues and its overexpression was positively correlated with poor prognosis and lymph node metastasis. CUL4B knockdown in GC cells decreased proliferation, mesenchymal transition and invasion in vitro, as well as tumor growth and metastasis in nude mice, and CUL4B overexpression induced the opposite results. Further studies showed that miR-101 could inhibit CUL4B expression by directly targeting its 3’-UTR and they were inversely correlated in clinical GC specimens. Notably, a positive relationship between CUL4B and HER2 was found in GC clinical specimens, GC cells and GC xenograft tumors. Through bioinformatics analysis of miRNA-seq data and target prediction, we nominated miR-125a as a direct target of CUL4B. ChIP assays demonstrated that CUL4B directly repressed miR-125a expression by physically binding to its promoter. In addition, we confirmed miR-125a is the target of HER2. Consequently, we demonstrated that CUL4B can up-regulate HER2 expression through repressing miR-125a. Most importantly, silencing of HER2 by Herceptin or siRNA partially reversed CUL4B-induced epithelial-to-mesenchymal transition (EMT), cell invasion and metastasis in vitro and in vivo. These findings define a CUL4B-miR-125a-HER2 regulatory mechanism shed light on CUL4B oncogenic mechanisms and reveals promising therapeutic targets for progressive GC. CUL4B proteins are frequently upregulated in human cancer, yet little is known about the underlying molecular mechanisms of CUL4B induced gastric cancer(GC) carcigenesis.Here, we uncover the critical role of CUL4B in gastric cancer growth and metastasis through the regulation of HER2 expression.CUL4B contributes to GC invasion and metastasis by transcriptional repression of HER2 targeting miR-125a, which provide a new insight into how CUL4B regulates GC progression and metastasis.
2017-11-25 | GSE90501 | GEO
Project description:It has been reported that PHF1, CUL4B and PRMT5 all play important roles in epigenetic regulation. We reported that PHF1, CRL4B and PRMT5 may act as a complex in transcriptional regulation and have a vital effect in breast cancer progression. So we performed ChIP-on-chip assays to find unique promoters co-targeted by PHF1, CUL4B and PRMT5. PHF1, CUL4B and PRMT5 have a predominant cooperation, at least in MDA-MB-231 cells. comparison of PHF1, CUL4B and PRMT5 target genes
2016-07-07 | E-GEOD-84071 | biostudies-arrayexpress
Project description:It has been reported that PHF1, CUL4B and PRMT5 all play important roles in epigenetic regulation. We reported that PHF1, CRL4B and PRMT5 may act as a complex in transcriptional regulation and have a vital effect in breast cancer progression. So we performed ChIP-on-chip assays to find unique promoters co-targeted by PHF1, CUL4B and PRMT5. PHF1, CUL4B and PRMT5 have a predominant cooperation, at least in MDA-MB-231 cells.
2016-07-07 | GSE84071 | GEO
Project description:Breast Cancer is the cancer with most incidence and mortality in women. microRNAs are emerging as novel prognosis/diagnostic tools. Our aim was to identify a serum microRNA signature useful to predict cancer development. We focused on studying the expression levels of 30 microRNAs in the serum of 96 breast cancer patients versus 92 control individuals. Bioinformatic studies provide a microRNA signature, designated as a predictor, based upon the expression levels of 5 microRNAs. Then, we tested the predictor in a group of 60 randomly chosen women. Lastly, a proteomic study unveiled the over-expression and down-regulation of proteins differently expressed in the serum of breast cancer patients versus that of control individuals. Twenty-six microRNAs differentiate cancer tissue from healthy tissue and 16 microRNAs differentiate the serum of cancer patients from that of the control group. The tissue expression of miR-99a-5p, mir-497-5p, miR-362, and miR-1274, and the serum levels of miR-141 correlated with patient survival. Moreover, the predictor consisting of mir-125b-5p, miR-29c-3p, mir-16-5p, miR-1260, and miR-451a was able to differentiate breast cancer patients from controls. The predictor was validated in 20 new cases of breast cancer patients and tested in 60 volunteer women, assigning 11 out of 60 women to the cancer group. An association of low levels of mir-16-5p with a high content of CD44 protein in serum was found. Circulating microRNAs in serum can represent biomarkers for cancer prediction. Their clinical relevance and use of the predictor here described might be of potential importance for breast cancer prediction.
2020-09-18 | PXD020795 | Pride
Project description:Cullin 4B (CUL4B) is a scaffold protein of the CUL4B-Ring E3 ligase (CRL4B) complex. Here, we found that CRL4B interacted with transcriptional corepressor complexes. Our results supporting CUL4B as a potential target of cancer therapy.
2021-03-25 | GSE124611 | GEO
Project description:We used a genome-wide approach (High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation, or HITS-CLIP) to define direct miRNA-mRNA interactions in three breast cancer subtypes (estrogen receptor positive, Her2 amplified and triple negative). Focusing on steroid receptor signaling, we identified two novel regulators of the ER pathway (miR-9-5p and miR-193a/b-3p), which together target multiple genes involved in ER signaling. Moreover, this approach enabled the definition of miR-9-5p as a global regulator of steroid receptor signaling in breast cancer. Finally, we show that miRNA targets and networks defined by our analysis are predictive of patient outcomes and provide global insight into miRNA regulation in breast cancer. Argonaute HITS-CLIP on three representative breast cancer cell lines (each in triplicate).
2014-08-04 | E-GEOD-57855 | biostudies-arrayexpress
Project description:Tamoxifen (TAM) is the frontline therapy for estrogen receptor-positive (ER+) breast cancer in premenopausal women that interrupts ER signaling. As tumors with elevated heterogeneity, amounts of ER-negative (ER-) cells are present in ER+ breast cancer that cannot be directly killed by TAM. Despite complete remissions have been achieved in clinical practice, the mechanism underlying the elimination of ER- cells during TAM treatment remains an open issue. Herein, we deciphered the elimination of ER- cells in TAM treatment from the perspective of the bystander effect. Markable reductions were observed in tumorigenesis of ER- breast cancer cells by applying both supernatants from TAM-treated ER+ cells and a transwell co-culture system, validating the presence of a TAM-induced bystander effect. The major antitumor protein derived from ER- cells, peptidyl-prolyl cis-trans isomerase B (PPIB), is the mediator of the TAM-induced bystander effect identified by quantitative proteomics. The attenuation of ER- cells was attributed to activated BiP/eIF2α/CHOP axis and promoted endoplasmic reticulum stress (ERS)-induced apoptosis, which can also be triggered by PPIB independently. Altogether, our study revealed a novel TAM-induced bystander effect in TAM treatment of ER+ breast cancer, raising the possibility to develop PPIB as a synergistic antitumor agent or even substitute endocrine therapy.
2024-02-12 | GSE247920 | GEO
Project description:We used a genome-wide approach (High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation, or HITS-CLIP) to define direct miRNA-mRNA interactions in three breast cancer subtypes (estrogen receptor positive, Her2 amplified and triple negative). Focusing on steroid receptor signaling, we identified two novel regulators of the ER pathway (miR-9-5p and miR-193a/b-3p), which together target multiple genes involved in ER signaling. Moreover, this approach enabled the definition of miR-9-5p as a global regulator of steroid receptor signaling in breast cancer. Finally, we show that miRNA targets and networks defined by our analysis are predictive of patient outcomes and provide global insight into miRNA regulation in breast cancer.
2014-08-04 | GSE57855 | GEO
Project description:Cancer stem-like traits contribute to prostate cancer (PCa) progression and metastasis. Discovering and clarifying the underlying molecular mechanisms associated with PCa stem-like traits would be great beneficial to clinical treatment of advanced PCa. Cullin 4B (CUL4B) is a scaffold protein overexpressed in several solid malignancies. It is known to silence tumor suppressor through post-transcriptional manner. In this study, through gain- and loss-of-function experiments, we showed that CUL4B promotes PCa pluripotency-associated markers expression, sphere formation and anchorage-independent growth ability in virto. Mechanically, we identified BMI1 as a target of CUL4B. CUL4B unregulates BMI1 expression via epigenetically repressing microRNA-200b (miR200b) and microRNA-200c (miR200c). In addition, miR200b and miR200c (miR200b/c) could partially reverse CUL4B-induced BMI1 and pluripotency-associated marker expression. Finally, our study revealed a CUL4B-miR200b/c-BMI1 oncoprotein axis in PCa, which might give novel insight into how CUL4B promotes PCa progression through regulating cancer stem-like traits.
2019-04-13 | GSE129739 | GEO
Project description:microRNA (miRNA) dysfunction is associated with a variety of human diseases including cancer. Our previous study showed that miR-671-5p was deregulated during breast cancer progression. We aim to decipher the functional mechanism of miR- 671-5p in breast cancer. We used microarrays to detail the global programme of gene expression after overexpression miR-671-5p in several breast cancer cell lines, and those altered genes might potentially under regulation of miR-671-5p contibuting to breast cancer developemtn. miR-671-5p or scramble control nucleotide were tranfected into breast cancer cell lines, including MCF7, MDA231 and SKBR3. Total RNA were extracted and hybridized on Affymetrix microarrays. We sought to identify the potential downstream target genes that under miR-671-5p regulation by overexpress miR-671-5p. Potential targets were predicted to see if it has binding sites matching miR-671-5p sequence by miRNA target prediction softwares.
2014-10-16 | E-GEOD-62411 | biostudies-arrayexpress