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Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [RBM47 KD]

ABSTRACT: RBM47 is a RNA binding protein that is known to regulate alternative splicing. To study the genome wide regulatory role of RBM47 in alternative splicing and determine the potential function of RBM47 during EMT, we used lentiviral shRNAs to knockdown RBM47 in H358 cells and performed RNA-seq in biological triplicates.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75491 | GEO | 2016/04/05

SECONDARY ACCESSION(S): PRJNA304418

REPOSITORIES: GEO

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Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [RBM47 KD]

Project description:RBM47 is a RNA binding protein that is known to regulate alternative splicing. To study the genome wide regulatory role of RBM47 in alternative splicing and determine the potential function of RBM47 during EMT, we used lentiviral shRNAs to knockdown RBM47 in H358 cells and performed RNA-seq in biological triplicates. We used lentiviral based shRNAs to knockdown RBM47 in human H358 cells. We harvested total RNA and protein from RBM47 knockdown and control knockdown in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.

2016-04-05 | E-GEOD-75491 | biostudies-arrayexpress

Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [ESRP KD]

Project description:Epithelial specific splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) are important regulators of alternative splicing during EMT. To study the alternative splicing events regulated by ESRP1/2 at a genome wide scale, we used lentiviral shRNAs to knockdown ESRP1/2 in H358 cells and performed RNA-seq in biological triplicates. We used lentiviral based shRNAs targeting ESRP1 and ESRP2 to knockdown both regulators in human H358 cells. We harvested total RNA and protein from ESRP1/2 knockdown and control knockdown in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.

2016-04-05 | E-GEOD-75489 | biostudies-arrayexpress

Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [ESRP KD]

2016-04-05 | GSE75489 | GEO

RNA-binding Motif Protein RBM47 Promotes Tumorigenesis in Nasopharyngeal Carcinoma through Multiple Pathways

Project description:ABSTRACT RNA binding motif proteins (RBMs) have been widely implicated in the tumorigenesis of multiple human cancers, but scarcely studied in nasopharyngeal carcinoma (NPC). Here, we compare the mRNA levels of 29 RBMs between 87 NPC and 10 control samples. We find that RBM47 is frequently upregulated in NPC specimens and its high expression is associated with poor prognosis of patients with NPC. Biological experiments show that RBM47 plays an oncogenic role in NPC cells. Mechanically, RBM47 binds to the promoter and regulates the transcription of BCAT1 and its overexpression partially rescues the inhibitory effects of RBM47-knockdown on NPC cells. Moreover, transcriptome analysis reveals that RBM47 regulates alternative splicing of pre-mRNA, including those cancer-related, to a large extent in NPC cells. Furthermore, RBM47 binds to hnRNPM and cooperativelyjointly regulates multiple splicing events in NPC cells. In addition, we find that knockdown of hnRNPM inhibits proliferation and migration of NPC cells. Taken together, our study shows that RBM47 promotes the progression of NPC through multiple pathways, acting as a transcriptional factor and a modulator of alternative splicing in cooperation with hnRNPM. Our study also highlights that RBM47 and hnRNPM could be prognostic factors and potential therapeutic targets for NPC. Keywords RBM47, BCAT1, Alternative splicing, hnRNPM, Nasopharyngeal Carcinoma (NPC)

2022-06-01 | GSE176549 | GEO

Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [EMT.time course]

Project description:The epithelial to mesenchymal transition (EMT) is an essential biological process during embryonic development and has also been implicated in cancer metastasis. Previous studies have characterized transcriptional regulation and key transcription factors that impact EMT. However, the role of alternative splicing (AS) regulation in EMT has only recently emerged and remains relatively uncharacterized. Here we used a robust in vitro EMT model to dynamically and comprehensively characterize splicing switches during EMT in a temporal manner. We generated a H358 clone stably expressing a doxycycline (Dox)-inducible cDNA encoding a Zeb1-mCherry fusion protein. Over a 7-day time course following Dox treatment, cells have undergone EMT. We harvested total RNA and protein at each day of the EMT time course and a no Dox-treated control in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.

2016-04-05 | E-GEOD-75487 | biostudies-arrayexpress

Comparative gene expression profiling in small intestinal mucosa of Rbm47 intestine-specific knock-out and wt mice

Project description:Rationale: RNA binding protein 47 (RBM47) is required for embryonic endoderm development but a role in adult intestine is unknown. Objective: We studied intestine-specific Rbm47 knockout mice (Rbm47-IKO) following intestinal injury and made crosses into Apcmin/+ mice to examine alterations in intestinal proliferation, response to injury and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue. Findings: Rbm47-IKO mice exhibit increased proliferation, abnormal villus morphology and cellularity, with corresponding changes in Rbm47-IKO organoids. Rbm47-IKO mice adapt to radiation injury and are protected against chemical-induced colitis, with Rbm47-IKO intestine showing upregulation of antioxidant and Wnt signaling pathways as well as stem cell and developmental genes. Furthermore, Rbm47-IKO mice are protected against colitis-associated cancer. By contrast, aged Rbm47-IKO mice develop spontaneous polyposis and Rbm47-IKO, Apcmin/+ mice manifest an increased intestinal polyp burden. RBM47 mRNA was decreased in human colorectal cancer versus paired normal tissue along with alternative splicing of TJP1 mRNA. Public databases revealed stage-specific reduction in RBM47 expression in colorectal cancer, associated independently with decreased overall survival. Conclusions: These findings implicate RBM47 as a cell-intrinsic modifier of intestinal growth, inflammatory and tumorigenic pathways.

2023-05-31 | GSE206461 | GEO

Identification of alternatively spliced transcripts in brain metastatic derivatives of MDA-MB-231 breast cancer cells in response to RBM47 expression

2014-06-11 | GSE58379 | GEO

Identification of alternatively spliced transcripts in brain metastatic derivatives of MDA-MB-231 breast cancer cells in response to RBM47 expression

Project description:Changes in alternative splicing in breast cancer cells expressing control, empty vector or Flag-tagged wild type RBM47 were analyzed using paired-end, 100bp RNAseq. Related data published together with these data are found in GSE53779 Triplicate RNAseq libraries were prepared from non-clonal brain metastatic breast cancer cells stably expressing empty-vector, and a clonal cell line (wt#10) expressing Flag-tagged, wild-type RBM47 under a doxycline-inducible promoter, both treated for three days with doxycycline to induce transgene expression

2014-06-11 | E-GEOD-58379 | biostudies-arrayexpress

The RNA-binding protein RBM47 suppresses metastatic breast cancer progression

Project description:Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we have identified RNA binding motif protein 47 (RBM47) as a candidate suppressor of breast cancer metastasis. RBM47 inhibited breast cancer progression in experimental models. Transcriptome-wide analysis of RBM47 localization by HITS-CLIP revealed widespread binding to mRNAs, preferentially at the 3' UTRs. RBM47 altered the abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1 (DKK1), mediate tumor suppressive effects downstream of RBM47. This work identifies RBM47 as a suppressor of breast cancer progression and highlights the potential of global RNA modulatory events as a source of metastasis-promoting phenotypic traits.

2014-06-11 | GSE53779 | GEO

The RNA-binding protein RBM47 suppresses metastatic breast cancer progression

2014-06-11 | E-GEOD-53779 | biostudies-arrayexpress