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Prp19 is an independent prognostic marker and promotes neuroblastoma metastasis by regulating the Hippo-YAP signaling pathway [SK-N-AS]

ABSTRACT: Prp19 is an independent prognostic marker and promotes neuroblastoma metastasis by regulating the Hippo-YAP signaling pathway [SK-N-AS]

PROVIDER: PRJNA642643 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12103712_1.fastq.gz	Fastqsanger.gz
	SRR12103712_2.fastq.gz	Fastqsanger.gz
	SRR12103713_1.fastq.gz	Fastqsanger.gz
	SRR12103713_2.fastq.gz	Fastqsanger.gz
	SRR12103714_1.fastq.gz	Fastqsanger.gz

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Prp19 is an independent prognostic marker and promotes neuroblastoma metastasis by regulating the Hippo-YAP signaling pathway [SK-N-AS]

Project description:This study first reveals that Prp19 is a potential oncogene in neuroblastoma, which is significantly correlated with poor prognosis and promote metastasis viaregulating Hippo-YAP pathway

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Prp19 is an independent prognostic marker and promotes neuroblastoma metastasis by regulating the Hippo-YAP signaling pathway [SK-N-BE(2)]

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Prp19 is an independent prognostic marker and promotes neuroblastoma metastasis by regulating the Hippo-YAP signaling pathway [SK-N-BE(2)]

Project description:Prp19 is an independent prognostic marker and promotes neuroblastoma metastasis by regulating the Hippo-YAP signaling pathway [SK-N-BE(2)]

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LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker.

Project description:There is a pressing need to identify prognostic markers of metastatic disease and targets for treatment. Combining high-throughput RNA sequencing, functional characterization, mechanistic studies and clinical validation, we identify leukemia inhibitory factor receptor (LIFR) as a breast cancer metastasis suppressor downstream of the microRNA miR-9 and upstream of Hippo signaling. Restoring LIFR expression in highly malignant tumor cells suppresses metastasis by triggering a Hippo kinase cascade that leads to phosphorylation, cytoplasmic retention and functional inactivation of the transcriptional coactivator YES-associated protein (YAP). Conversely, loss of LIFR in nonmetastatic breast cancer cells induces migration, invasion and metastatic colonization through activation of YAP. LIFR is downregulated in human breast carcinomas and inversely correlates with metastasis. Notably, in approximately 1,000 nonmetastatic breast tumors, LIFR expression status correlated with metastasis-free, recurrence-free and overall survival outcomes in the patients. These findings identify LIFR as a metastasis suppressor that functions through the Hippo-YAP pathway and has significant prognostic power.

| S-EPMC3684419 | biostudies-literature

Prp19 Is an Independent Prognostic Marker and Promotes Neuroblastoma Metastasis by Regulating the Hippo-YAP Signaling Pathway.

Project description:Pre-mRNA processing factor 19 (Prp19) was previously reported to be involved in tumor progression. However, Prp19 expression and its functions remain elusive in neuroblastoma. Here, we aim to identify the functions and mechanisms of Prp19 in neuroblastoma. Neuroblastic tumor tissue microarrays and two independent validation data sets indicate that Prp19 is associated with high-risk markers and bone marrow metastasis and serves as a prognostic marker for worse clinical outcomes with neuroblastoma. Gain- and loss-of-expression assays reveal that Prp19 promotes invasion, migration, and epithelial-mesenchymal transition (EMT) of neuroblastoma cells in vitro. Bioinformatics analysis of RNA-seq data shows that the expressions of YAP and its downstream genes are significantly inhibited after downregulation of Prp19. Prp19 and YAP expression in metastatic lymph nodes is higher than in situ neuroblastoma tissue. Further experiments show that Prp19 regulates YAP expression and consequently affects cell invasion, migration, and EMT in neuroblastoma by pre-mRNA splicing of YAP. In conclusion, our findings provide the first evidence that Prp19 is a potential therapeutic target and prognostic biomarker for patients with neuroblastoma.

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Gene expression profile of YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line (SK-Hep1)

Project description:Hippo signaling pathway is pivotally involved in human cancer. Among the Hippo components, YAP1 is highly active while function of MST1,2 and SAV1 was lost in liver cancer. Based on systematic analysis, we identified KLF5 as YAP1 binding partner in silico. To investigate KLF5 in liver cancer, we performed the gene expression microarray after knocked down YAP1, TEAD1 and KLF5 in SK-Hep1 cell line. To identify the role of YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line, we performed microarray after knocking down YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line (3 siLuc, 3 siYAP1, 3 siTEAD1, 3 siKLF5)

2013-12-31 | E-GEOD-32597 | biostudies-arrayexpress

A splicing switch of TEAD4 regulates Hippo-YAP signaling pathway to inhibit tumor proliferation

Project description:Splicing dysregulations extensively occur in cancers, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signaling, a key pathway that regulates cell proliferation and organ size, is under control of a new splicing switch. We show that TEAD4, the transcription factor that mediates Hippo-YAP signaling, undergoes alternative splicing facilitated by the tumor suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks N-terminal DNA-binding domain but maintains YAP-interaction domain. TEAD4-S is located in both nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumor growth in xenograft mouse model. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether these data reveal a novel RBM4-mediated splicing switch that serves to fine-tune Hippo-YAP pathway. Cell lines stably expressing YAP, YAP/TEAD4-S, YAP/TEAD4-FL, YAP/RBM4 and control vector were created, and the total RNA was purified from the cells using TRIzol reagents. The polyadenylated RNAs were purified for construction of sequencing library using kapa TruSeq Total RNA Sample Prep kits (UNC High Throughput Sequencing Facility).

2016-06-16 | E-GEOD-80372 | biostudies-arrayexpress

DHODH is an independent prognostic marker and potent therapeutic target in neuroblastoma

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