The RNA-binding protein ESRP1 modulates the expression of RAC1b in colorectal cancer cells [COLO320DM]
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ABSTRACT:
PROVIDER: PRJNA746597 | ENA |
REPOSITORIES: ENA
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Project description:Colorectal cancer (CRC) ranks third for incidence and second for number of deaths among cancer types worldwide. Poor patient survival, due to inadequate response to currently available treatment regimens, points out to the urgent requirement for personalized therapy in CRC patients. Our aim was to provide mechanistic insights into the pro-tumorigenic role of the RNA-binding protein ESRP1, which is highly expressed in a subset of CRC patients. We show that, in CRC cells, ESRP1 binds to and has the same trend in expression as RAC1b, a well-known tumor promoter. Thus, RAC1b may be a potential therapeutic target in ESRP1-overexpressing CRC. RNA binding proteins are well recognized as critical regulators of tumorigenic processes through their capacity to modulate RNA biogenesis, including alternative splicing, RNA stability and mRNA translation. The RNA binding protein Epithelial Splicing Regulatory Protein 1 (ESRP1) can act as tumor suppressor or promoter in a cell type- and disease context-dependent manner. We have previously shown that elevated expression of ESRP1 in colorectal cancer cells can drive tumor progression. To gain further insights into the pro-tumorigenic mechanism of action of ESRP1, we performed cDNA microarray analysis on two colorectal cells lines modulated for ESRP1 expression. Intriguingly, RAC1b was highly expressed, both at mRNA and protein levels, in ESRP1-overexpressing cells, while the opposite trend was observed in ESRP1-silenced CRC cells. Moreover, RAC1 and RAC1b mRNA co-immunoprecipitate with ESRP1 protein. Silencing of RAC1b expression significantly reduced the number of soft agar colonies formed by ESRP1-overexpressing cells, suggesting that ESRP1 acted, at least partially, through RAC1b in its tumor-promoting activities in CRC cells. Thus, our data provide molecular cues on targetable candidates in CRC cases with high ESRP1 expression.
2021-08-31 | GSE180126 | GEO
Project description:Colorectal cancer (CRC) ranks third for incidence and second for number of deaths among cancer types worldwide. Poor patient survival, due to inadequate response to currently available treatment regimens, points out to the urgent requirement for personalized therapy in CRC patients. Our aim was to provide mechanistic insights into the pro-tumorigenic role of the RNA-binding protein ESRP1, which is highly expressed in a subset of CRC patients. We show that, in CRC cells, ESRP1 binds to and has the same trend in expression as RAC1b, a well-known tumor promoter. Thus, RAC1b may be a potential therapeutic target in ESRP1-overexpressing CRC. RNA binding proteins are well recognized as critical regulators of tumorigenic processes through their capacity to modulate RNA biogenesis, including alternative splicing, RNA stability and mRNA translation. The RNA binding protein Epithelial Splicing Regulatory Protein 1 (ESRP1) can act as tumor suppressor or promoter in a cell type- and disease context-dependent manner. We have previously shown that elevated expression of ESRP1 in colorectal cancer cells can drive tumor progression. To gain further insights into the pro-tumorigenic mechanism of action of ESRP1, we performed cDNA microarray analysis on two colorectal cells lines modulated for ESRP1 expression. Intriguingly, RAC1b was highly expressed, both at mRNA and protein levels, in ESRP1-overexpressing cells, while the opposite trend was observed in ESRP1-silenced CRC cells. Moreover, RAC1 and RAC1b mRNA co-immunoprecipitate with ESRP1 protein. Silencing of RAC1b expression significantly reduced the number of soft agar colonies formed by ESRP1-overexpressing cells, suggesting that ESRP1 acted, at least partially, through RAC1b in its tumor-promoting activities in CRC cells. Thus, our data provide molecular cues on targetable candidates in CRC cases with high ESRP1 expression.
2021-08-31 | GSE180125 | GEO
Project description:The RNA-binding protein ESRP1 modulates the expression of RAC1b in colorectal cancer cells [HCA24]
| PRJNA746596 | ENA
Project description:Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific RBP and splicing factor. Both a tumor suppressor role and a pro-metastatic function of ESRP1 have been reported.Our aim was to clarify the role of ESRP1 in colorectal cancer setting.We employed both loss-of-function and gain-of-function approaches to study the role of ESRP1 in human colorectal tumorigenesis in vitro and in vivo, as well as in the metastatic process in vivo.
2016-12-31 | GSE81894 | GEO
Project description:The epithelial splicing regulatory proteins, ESRP1 and ESRP2 are essential for mammalian development through regulation of a global program of alternative splicing of genes involved in maintenance of epithelial cell function. To further inform our understanding of the molecular functions of ESRP1 we performed enhanced crosslinking immunoprecipitation coupled with high throughput sequencing (eCLIP) in epithelial cells of mouse epidermis. The genome-wide binding sites of ESRP1 were integrated with RNA-Seq analysis of alterations in splicing and total gene expression that result from epidermal ablation of Esrp1 and Esrp2. These studies demonstrated that ESRP1 functions in splicing regulation occur primarily through direct binding in a position-dependent manner to either promote exon inclusion or skipping. In addition, we also identified widespread binding of ESRP1 in 3’ and 5’ untranslated regions (UTRs) of genes involved in epithelial cell function, suggesting that its post-transcriptional functions extend beyond splicing regulation.
2022-09-12 | GSE212304 | GEO
Project description:RNA binding proteins are well recognized as critical regulators of tumorigenic processes through their capacity to modulate RNA biogenesis, including alternative splicing, RNA stability and mRNA translation. The RNA binding protein Epithelial Splicing Regulatory Protein 1 (ESRP1) can act as a tumor suppressor or promoter in a cell type- and disease context-dependent manner. We have previously shown that elevated expression of ESRP1 in colorectal cancer cells can drive tumor progression. To gain further insights into the pro-tumorigenic mechanism of action of ESRP1, we performed cDNA microarray analysis on two colorectal cells lines modulated for ESRP1 expression. Intriguingly, RAC1b was highly expressed, both at mRNA and protein levels, in ESRP1-overexpressing cells, while the opposite trend was observed in ESRP1-silenced CRC cells. Moreover, RAC1 and RAC1b mRNA co-immunoprecipitate with ESRP1 protein. Silencing of RAC1b expression significantly reduced the number of soft agar colonies formed by ESRP1-overexpressing cells, suggesting that ESRP1 acted, at least partially, through RAC1b in its tumor-promoting activities in CRC cells. Thus, our data provide molecular cues on targetable candidates in CRC cases with high ESRP1 expression.
| S-EPMC8392041 | biostudies-literature
Project description:ESRP1 is an epithelial-specific splicing factor. It mainly regulates expressions of genes related to intercellular adhesion, actin cytoskeleton, cell polarity and cell migration at the post-transcriptional level by alternative splicing. It also plays an important role in the development and progression of cancers. This study analyzed the transcriptome changes of ESRP1 stably overexpression SKOV3 cells by high-throughput sequencing, discovered and validated the functional effects of ESRP1 on ovarian cancer cells
2020-05-21 | GSE133841 | GEO
Project description:RNA-binding proteins and their mediated alternative splicing play important roles in tumor cell invasion and migration. Here, we report that ESRP1 is a key regulator of gastric cancer cell metastasis. Overexpression of ESRP1 inhibits the invasion and migration of gastric cancer cells, in vivo and in vitro. Furthermore, we found that ESRP1 causes a wide range of alternative splicing events, and ESRP1-mediated CLSTN1 exon skipping may be a key mechanism for its inhibition of gastric cancer cell invasion and metastasis. Taken together, our data provide a molecular framework for the role of ESRP1 in gastric cancer development.
2023-12-27 | GSE233685 | GEO
Project description:Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific RNA binding protein that controls several key cellular processes, like alternative splicing and translation. Previous studies have demonstrated a tumor suppressor role for this protein. Recently, however, a pro-metastatic function of ESRP1 has been reported. We thus aimed at clarifying the role of ESRP1 in Colorectal Cancer (CRC) by performing loss- and gain-of-function studies, and evaluating tumorigenesis and malignancy with in vitro and in vivo approaches. We found that ESRP1 plays a role in anchorage-independent growth of CRC cells. ESRP1-overexpressing cells grown in suspension showed enhanced fibroblast growth factor receptor (FGFR1/2) signalling, Akt activation, and Snail upregulation. Moreover, ESRP1 promoted the ability of CRC cells to generate macrometastases in mice livers. High ESRP1 expression may thus stimulate growth of cancer epithelial cells and promote colorectal cancer progression. Our findings provide mechanistic insights into a previously unreported, pro-oncogenic role for ESRP1 in CRC, and suggest that fine-tuning the level of this RNA-binding protein could be relevant in modulating tumor growth in a subset of CRC patients.
| S-EPMC5354637 | biostudies-literature
Project description:RNA-binding proteins and their mediated alternative splicing play important roles in tumor cell invasion and migration. Here, we report that ESRP1 is a key regulator of gastric cancer cell metastasis. Overexpression of ESRP1 inhibits the invasion and migration of gastric cancer cells, in vivo and in vitro. Through crosslinking-immunoprecipitation and high-throughput sequencing (CLIP seq), we revealed that ESRP1 binding to the CLSTN1 mRNA and mediated its exon skipping, which may be a key mechanism for its inhibition of gastric cancer cell invasion and metastasis. Taken together, our data provide a molecular framework for the role of ESRP1 in gastric cancer development.
2023-12-27 | GSE233931 | GEO