KH-type splicing regulatory protein (KHSRP) is involved in esophageal squamous cell carcinoma progression through regulating a subset of microRNAs [miRNA]
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ABSTRACT: KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein (RBP), which is involved in many post-transcriptional aspects of RNA metabolism including microRNA (miRNA) biogenesis, affects distinct cell functions in different tissues and can impact on various pathological conditions. However, the function and underlying mechanisms of KHSRP in esophageal squamous cell carcinoma (ESCC) remain largely unknown. In the present study, we uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC.
Project description:KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein (RBP), which is involved in many post-transcriptional aspects of RNA metabolism including microRNA (miRNA) biogenesis, affects distinct cell functions in different tissues and can impact on various pathological conditions. However, the function and underlying mechanisms of KHSRP in esophageal squamous cell carcinoma (ESCC) remain largely unknown. In the present study, we uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC.
Project description:KH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein. KHSRP regulates transcription, mRNA decay and translation, and miRNA biogenesis that influence distinct functions associated with cancer cell biology, such as inflammation and cell-fate determination. Our study uncovered novel mechanistic-based data on the tumor-promoting effects of KHSRP in colorectal cancer. We used microarrays to detail changes in gene expression upon specific knockdown of KHSRP in SW480 cells
Project description:KH-type splicing regulatory protein (KHSRP) is involved in esophageal squamous cell carcinoma progression through regulating a subset of microRNAs
Project description:KH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein. KHSRP regulates transcription, mRNA decay and translation, and miRNA biogenesis that influence distinct functions associated with cancer cell biology, such as inflammation and cell-fate determination. However, the role KHSRP plays in colorectal cancer (CRC) tumorigenesis is largely unknown. Our study uncovered novel mechanistic-based data on the tumor-promoting effects of KHSRP in CRC, including the control by KHSRP of protein secreted by CRC epithelial cells, influencing the tumor-promoting microenvironment.
Project description:We report KH-type splicing regulatory protein (KHSRP) as a novel m6A reader with oncogenic functions in pancreatic ductal adenocarcinoma (PDAC). KHSRP recognizes and stabilizes its target mRNAs (e.g., MET, ITGAV and ITGB1) in an m6A-dependent manner, therefore activating downstream FAK signaling and promoting PDAC progression. Targeting KHSRP shows promising anti-tumoral effects in vitro and in vivo, indicating that KHSRP may serve as a therapeutic target for PDAC.
Project description:Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC). Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis. We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis.
Project description:Our aim is to identify frequent genomic aberrations both in ESCC and esophageal dysplasia, and to discover important copy number-driving genes and microRNAs in ESCC. We carried out array-based comparative genomic hybridization (array CGH) on 59 ESCC resection samples and 16 dysplasia biopsy samples. Expression of genes at 11q13.3 was analyzed by real-time PCR and immunohistochemistry (IHC). Integrated analysis was performed to identify genes or microRNAs with copy number-expression correlations. Two group experiment, esophageal dysplasia vs. esophageal squamous cell carcinoma. Biological replicates: 16 dysplasias vs. 59 carcinomas
Project description:Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC). Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis. We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis.
Project description:Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC). Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis. We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis.
Project description:Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC). Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis.