Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy

ABSTRACT: OSCC is a common cancer of the head and neck. Despite ongoing efforts, there remains a dearth of targeted drugs capable of effectively inhibiting OSCC growth. As the earliest discovered proto-oncogene in the SRSF family, targeted inhibition of SRSF1 plays an important role in tumor suppression. However, a comprehensive report on the expression, function, and mechanism of SRSF1 in OSCC has yet to be presented. This study retrospectively analyzed clinical samples from OSCC patients and discovered a significant correlation between the SRSF1 expression level and poor prognosis. In vitro experimentation demonstrated that SRSF1 knockdown inhibited OSCC growth, survival, lysosomal biogenesis and autophagy. To confirm the significance of lysosomal function and autophagy in the regulation of OSCC growth by SRSF1, cell rescue models were constructed. The aforementioned findings were subsequently validated in xenograft models. Ultimately, targeted knockdown of SRSF1 was found to significantly suppress OSCC growth by impeding lysosomal biogenesis and autophagy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244710 | GEO | 2023/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy

Project description:Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy

| PRJNA1024425 | ENA

Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection

Project description:Lysosomal cathepsins regulate an exquisite range of biological functions, and their deregulation is associated with inflammatory, metabolic and degenerative disease in humans. Here, we identified a key cell-intrinsic role for cathepsin B as a negative feedback regulator of lysosomal biogenesis and autophagy. Mice and macrophages lacking cathepsin B activity had increased resistance to the cytosolic bacterial pathogen Francisella novicida. Genetic deletion or pharmacological inhibition of cathepsin B downregulated mTOR activity and prevented cleavage of the lysosomal calcium channel TRPML1. These events drove transcription of lysosomal and autophagy genes via the transcription factor TFEB, which increased lysosomal biogenesis and activation of autophagy-initiation kinase ULK1 for clearance of the bacteria. Our results identified a fundamental biological function of cathepsin B in providing a checkpoint for homeostatic maintenance of lysosome population and basic recycling functions in the cell. We used microarrays to explore the gene expression profiles differentially expressed in bone marrow-derived macrophages (BMDM) isolated from cathepsin B-/- and wild-type mice.

2016-08-04 | E-GEOD-79508 | biostudies-arrayexpress

ZKSCAN3 in the transcriptional regulation of autophagy in human cells

Project description:Transcription factors can affect autophagy activity by promoting or inhibiting the expression of autophagy and lysosomal related genes. As a zinc finger family DNA-binding protein, ZKSCAN3 has been reported to function as a transcriptional repressor of autophagy, silencing of which can induced autophagy and promoted lysosome biogenesis in cancer cells. However, the studies in Zkscan 3 knockout mice showed that the deficiency of Zkscan3 did not induce autophagy and in-crease lysosome biogenesis. In order to further explore the role of ZKSCAN3 in the transcriptional regulation of autophagy in human cells, we generated ZKSCAN3 knockout HK-2 and Hela cells by CRISPR/Cas9 system and analyzed the differences in gene expression between ZKSCAN3 deleted cells and non-deleted cells through fluorescence quantitative PCR, Western blot and transcriptome sequencing, with special attention to the differences in gene expression of autophagy and lysosomal biogenesis. We found that ZKSCAN3 is not an essential regulator of autophagic or lysosomal gene expression, as the absence ZKSCAN3 had no significantly effect on the expression of autophagy or lysosomal genes.

2023-01-31 | GSE218727 | GEO

Effect of SRSF1 splicing factor knockdown in the physiology and function of cytotoxic CD8 T lymphocytes and a potential molecular mechanism in viral immunopathogenesis

Project description:Cytotoxic CD8 T cells are crucial for the host antigen-specific immune response to viral pathogens. Here we report the identification of an essential role for the serine/arginine-rich splicing factor (SRSF) 1 in CD8 T cell homeostasis and function Transcriptomics analyses of Srsf1-deficient T cells reveal that SRSF1 controls cell cycle, MAP kinase signaling and IFN signaling pathways.

2022-07-31 | GSE201028 | GEO

Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection

2016-08-04 | GSE79508 | GEO

RNA-Seq Samples of siTFE3 in 8988T PDA Cell Line to Investigate Transcriptional Control of the Autophagy-Lysosome System

Project description:The activation of cellular quality control pathways to maintain metabolic homeostasis and mitigate diverse cellular stresses is emerging as a critical growth and survival mechanism in many cancers. Autophagy, a highly conserved cellular self-degradative process, is a key player in the initiation and maintenance of pancreatic ductal adenocarcinoma (PDA). However, the regulatory circuits that activate autophagy, and how they enable reprogramming of PDA cell metabolism are unknown. We now show that autophagy regulation in PDA occurs as part of a broader program that coordinates activation of lysosome biogenesis, function and nutrient scavenging, through constitutive activation of the MiT/TFE family of bHLH transcription factors. In PDA cells, the MiT/TFE proteins - MITF, TFE3 and TFEB - override a regulatory mechanism that controls their nuclear translocation, resulting in their constitutive activation. By orchestrating the expression of a coherent network of genes that induce high levels of lysosomal catabolic function, the MiT/TFE factors are required for proliferation and tumorigenicity of PDA cells. Importantly, unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosomal activation is specifically required to maintain intracellular AA pools in PDA. This AA flux is part of a program that is essential for metabolic homeostasis and bioenergetics of PDA but not for their non-transformed counterparts. These results identify the MiT/TFE transcription factors as master regulators of the autophagy-lysosomal system in PDA and demonstrate a central role of the autophagosome-lysosome compartment in maintaining tumor cell metabolism through alternative amino acid acquisition and utilization. Examination of mRNA levels in pancreatic ductal adenocarcinoma (PDA) cell line 8988T after treatment with siRNA for control or TFE3

2015-04-03 | E-GEOD-62077 | biostudies-arrayexpress

PAR-CLIP analysis of YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 and SRSF10 in human HeLa cells

Project description:Label the cells overexpressed Flag tagged YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 and SRSF10 with 4-SU, the RNA bound by YTHDC1 and SRSF proteins can be got by Flag IP followed by RNA isolation by using the TRIzol (Invitrogen) reagent by following the company manual.the RNA was then used for library preparation using a TruSeqâ¢ RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturerâs protocol.The libraries were sequenced using HiSeq2000 (Illumina) in single-read mode, creating reads with a length of 101 bp. Sequencing chemistry v2 (Illumina) was used and samples were multiplexed in two samples per lane. Discovery of the binding motif of YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 or SRSF10 in overexpressed Human HeLa cells

2016-02-17 | E-GEOD-71096 | biostudies-arrayexpress

Changes to the global transcriptome in human U2OS and BJ cell lines as a result of STING activation

Project description:Activation of Stimulator of interferon genes (STING) is well known to upregulate inflammation through canonical TBK1 signaling. STING is recently found to activate noncanonical functions through its transmembrane proton channel. Whether STING stimulates any transcription programs through its channel is unknown. In this study, we identified the transcription factor EB (TFEB) as a downstream effector of the STING channel. TFEB is a transcriptional regulator of lysosomal biogenesis and autophagy. Using RNA sequencing approaches, we confirmed that STING activated transcriptional upregulation of lysosomal biogenesis and autophagy independently of TBK1.

2024-09-19 | GSE254174 | GEO

Transcriptional regulation of the innate immune reponse by the MITF/TFE3 family

Project description:To understand the activation of the MITF/TFE transcription factors in effective defense against pathogens we examined the genome wide distribution of TFE3 in control and activated mouse macrophages. It was determined that TFEB and TFE3 collaborate with each other to promote efficient autophagy induction, increased lysosomal biogenesis, and transcriptional upregulation of proinflammatory cytokines and key mediators of the inflammatory response. 4 samples were analyzed: Background Control, Control, Starvation, LPS

2016-02-01 | E-GEOD-75822 | biostudies-arrayexpress

RNA-Seq Samples of siTFE3 in 8988T PDA Cell Line to Investigate Transcriptional Control of the Autophagy-Lysosome System

2015-04-03 | GSE62077 | GEO