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RNA helicase DDX5 mediates adaptive response to multi-kinase inhibitors in liver cancer

ABSTRACT: RNA helicase DDX5 mediates adaptive response to multi-kinase inhibitors in liver cancer

PROVIDER: PRJNA818332 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18401172_1.fastq.gz	Fastqsanger.gz
	SRR18401172_2.fastq.gz	Fastqsanger.gz
	SRR18401173_1.fastq.gz	Fastqsanger.gz
	SRR18401173_2.fastq.gz	Fastqsanger.gz
	SRR18401174_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

RNA helicase DDX5 mediates adaptive response to multi-kinase inhibitors in liver cancer

Project description:Earlier studies linked sorafenib effectiveness to induction of ferroptosis. Herein we demonstrate sorafenib and mTKIs downregulate DDX5 in vitro and in vivo. To understand the effect of DDX5 downregulation, we compared TCGA-derived HCCs expressing low vs. high DDX5 focusing on ferroptosis-related genes. Glutathione Peroxidase 4 (GPX4), a key ferroptosis regulator, was significantly overexpressed in DDX5LOW HCCs. Importantly, DDX5-knockdown (DDX5KD) HCC cell lines lacked lipid peroxidation by GPX4 inhibition, indicating DDX5 downregulation suppresses ferroptosis. RNAseq analyses comparing wild type vs. DDX5KD cells in the presence or absence of sorafenib, identified a unique set of genes repressed by DDX5 and upregulated by sorafenib. This set significantly overlaps genes from Wnt/β-catenin and non-canonical NF-κB pathways, including NF-κB inducing Kinase required for non-canonical NF-κB activation. Pharmacologic inhibition of these pathways in combination with sorafenib reduced DDX5KD cell viability. Mechanistically, sorafenib-mediated NF-κB activation induced NRF2 transcription, while DDX5KD extended NRF2 half/life by stabilizing p62/SQSTM1, leading to enhanced expression of GPX4 and ferroptosis escape. Conclusion: Sorafenib/mTKI-mediated DDX5 downregulation results in adaptive mTKI resistance by enhancing NRF2 expression, leading to ferroptosis escape. We propose inhibition of the pathways leading to NRF2 expression will enhance the therapeutic effectiveness of sorafenib/mTKIs.

2023-12-01 | GSE199092 | GEO

BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair

Project description:The BRCA2 tumor suppressor is a DNA double-strand break repair factor essential to maintain genome integrity. BRCA2-deficient cells spontaneously accumulate DNA-RNA hybrids, a known source of genome instability. However, the specific role of BRCA2 on these structures remains poorly understood. Here we identified the DEAD-box RNA helicase DDX5 as a BRCA2 interacting partner. We show that DDX5 associates with DNA-RNA hybrids that form in the vicinity of DSBs and this association is enhanced by BRCA2. Notably, BRCA2 stimulates the DNA-RNA hybrid helicase activity of DDX5. Impaired BRCA2-DDX5 interaction, as observed in cells bearing the breast cancer variant BRCA2-T207A, reduces DDX5 association with DSBs, decreases the number of RPA foci upon irradiation and impairs RAD51 repair foci formation. Our findings are consistent with DNA-RNA hybrids being an impediment for the repair of DSBs by homologous recombination and reveal BRCA2 and DDX5 as active players in their removal.

2021-02-26 | GSE150163 | GEO

The RNA helicase DDX5 supports mitochondrial function in small cell lung cancer

Project description:DDX5 is a founding member of the DEAD-box RNA helicase family, which are a group of enzymes that regulate ribonucleoprotein (RNP) formation and function in every aspect of RNA metabolism. Our lab previously found that DDX5 is involved in energy homeostasis, a process altered in many cancers. Small cell lung cancer (SCLC) is an understudied cancer type that lacks effective treatment. Therefore, we investigated the roles of DDX5 in SCLC. We show here that DDX5 is overexpressed in SCLC cell lines. Depletion of DDX5 results in reduced growth and mitochondrial dysfunction in the chemoresistant SCLC cell line H69AR. The latter is evidenced by downregulation of genes involved in oxidative phosphorylation and impaired oxygen consumption,. Interestingly, depletion of DDX5 specifically leads to reduction of intracellular succinate, a TCA intermediate that serves as a direct electron donor to mitochondrial complex II. Taken together, we propose that the oncogenic role of DDX5 is at least in part manifested through upregulation of respiration to support the energy demands of cancer cells. This also suggests that defects in RNP remodeling are connected to energy metabolism and carcinogenesis.

2020-05-06 | GSE142024 | GEO

Alternative splicing signatures in apoptosis related genes of human HeLa cells with RNAi targeting p68 RNA helicase-DDX5

Project description:Alternative splicing profiling of apopotosis related genes in human HeLa cells (cervical cancer cell line) transfected with a plasmid expressing shRNAs targetting p68 helicase (DDX5, DEAD (Asp-Glu-Ala-Asp) box polypeptide 5) cloned into the pSuper expression vector compared to empty vector. Keywords: treated vs. untreated comparison; alternative splicing Two-condition experiment, where the p68 DDX5 gene product levels was inhibited by siRNA transfection and compared to transfection with the negative control (scrambled siRNA). Biological replicates: 2, all independently grown and harvested. A dye swapping technical duplicate was performed for each biological replicate. Samples were hybridized onto a 44290 feature array designed by ExonHit to detect splicing events in apopotosis related genes and manufactured by Agilent using in situ synthesis of oligonucleotides by SurePrint technology.

2011-01-21 | E-GEOD-20010 | biostudies-arrayexpress

RNA helicase DDX5-induced circPHF14 promotes gastric cancer cell progression

Project description:RNA helicase DDX5-induced circPHF14 promotes gastric cancer cell progression

| PRJNA856484 | ENA

Alternative splicing signatures in apoptosis related genes of human HeLa cells with RNAi targeting p68 RNA helicase-DDX5

2011-01-21 | GSE20010 | GEO

The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs

Project description:N6-Methyladenosine (m6A) is well-known for controlling different processes of linear RNA metabolism. Conversely, its role in the biogenesis and function of circular RNAs (circRNAs) is still poorly understood. Here, we characterize circRNA expression in the pathological context of rhabdomyosarcoma (RMS), observing a global increase when compared to wild-type myoblasts. For a set of circRNAs, such an increase is due to the raised expression of the m6A machinery, which we also find to control the proliferation activity of RMS cells. Furthermore, we identify the RNA helicase DDX5 as a novel mediator of the back-splicing reaction and as a co-factor of the m6A regulatory network. DDX5 and the m6A reader YTHDC1 are shown to interact and to promote the production of a common subset of circRNAs in RMS. In line with the observation that YTHDC1/DDX5 depletion reduces RMS proliferation, our results provide proteins and RNA candidates for the study of rhabdomyosarcoma tumorigenicity.

2023-03-20 | GSE207453 | GEO

RNA helicase DDX21 mediates nucleotide stress responses

Project description:RNA helicase DDX21 mediates nucleotide stress responses

| PRJNA526370 | ENA

RNA helicase DDX5-induced circPHF14 promotes gastric cancer cell progression

Project description:To identify whether the expression of DDX5 was linked to circular RNAs splicing processes, we transfected AGS cell with FLAG-DDX5 or FLAG-tagged empty vector (negative control, NC), and analyzed the differentially expressed circRNAs

2023-04-26 | GSE207636 | GEO

RIP-seq of DDX5 in rhabdomyosarcoma cells

Project description:Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood characterized by the inability to exit the proliferative myoblast-like stage. Here, we identified the DEAD box RNA helicase 5 (DDX5) as a potential therapeutic target to inhibit alveolar rhabdomyosarcoma (ARMS) growth. We show that DDX5 is overexpressed in alveolar RMS cells, demonstrating that its depletion drastically decreases ARMS viability and slows tumor growth in xenograft models. Mechanistically, we provide evidence that DDX5 functions upstream the G9a/AKT survival signalling pathway, by modulating G9a protein stability

2022-08-22 | GSE175455 | GEO

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