Project description:RNA binding protein TIA1 cytoplasmic expression as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma (ESCC)
Project description:T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein modulating many regulatory aspects of target mRNA metabolism. Despite several reports referring to the role of TIA1 in carcinogenesis, little is known about the significance of its expression and function in human cancers including esophageal squamous cell carcinoma (ESCC). In the present study, we found that ectopic localization of overexpressed TIA1 in the cytoplasm was observed in a cohort of 143 ESCC patients using immunohistochemistry, and the cytoplasmic TIA1 was an independent prognosticator for worse overall survival. Moreover, we revealed that TIA1 was overexpression in many ESCC cell lines, and silencing of TIA1 in those cells inhibited cell growth with an accumulation of cells in G0âG1 and sub-G1 phases. The human TIA1 gene generates two major protein isoforms, TIA1a and TIA1b. Expression of TIA1a isoform tended to be higher than that of TIA1b in ESCC cells, and TIA1a was expressed both in the nucleus and cytoplasm but TIA1b was expressed mainly in the nucleus. Further studies revealed that each isoform showed opposite effects on cell proliferation through ectopically introducing each gene: TIA1a promotes anchorage-dependent and independent cell proliferation, whereas TIA1b inhibits cell proliferation and/or induces cell death. The ribonucleoprotein immunoprecipitation followed by a microarray analysis or massive-parallel sequencing identified a set of TIA1-associating mRNAs including enriched cell cycle-associated genes. Among them, SKP2 and CCNA2 mRNA were shown to be interacted with TIA1 protein through their different regions, and SKP2 and CCNA2 protein levels were positively regulated by TIA1 through suppression of mRNA decay and translational induction, respectively. These findings provide new insights into the previously unknown role of TIA1 and its isoforms as tumor-promoting molecules regulating a set of downstream oncogenic proteins, and implicate their potential application as a useful marker of malignant potential and a therapeutic target in ESCC. To investigate the target molecules regulated by TIA1 in esophageal squamous cell carcinoma cell line (KYSE180), the expression levels of mRNAs (total) and transcripts captured by RIP with TIA1 antibody (TIA1_RIP) were analyzed using microarray.
Project description:T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein modulating many regulatory aspects of target mRNA metabolism. Despite several reports referring to the role of TIA1 in carcinogenesis, little is known about the significance of its expression and function in human cancers including esophageal squamous cell carcinoma (ESCC). In the present study, we found that ectopic localization of overexpressed TIA1 in the cytoplasm was observed in a cohort of 143 ESCC patients using immunohistochemistry, and the cytoplasmic TIA1 was an independent prognosticator for worse overall survival. Moreover, we revealed that TIA1 was overexpression in many ESCC cell lines, and silencing of TIA1 in those cells inhibited cell growth with an accumulation of cells in G0–G1 and sub-G1 phases. The human TIA1 gene generates two major protein isoforms, TIA1a and TIA1b. Expression of TIA1a isoform tended to be higher than that of TIA1b in ESCC cells, and TIA1a was expressed both in the nucleus and cytoplasm but TIA1b was expressed mainly in the nucleus. Further studies revealed that each isoform showed opposite effects on cell proliferation through ectopically introducing each gene: TIA1a promotes anchorage-dependent and independent cell proliferation, whereas TIA1b inhibits cell proliferation and/or induces cell death. The ribonucleoprotein immunoprecipitation followed by a microarray analysis or massive-parallel sequencing identified a set of TIA1-associating mRNAs including enriched cell cycle-associated genes. Among them, SKP2 and CCNA2 mRNA were shown to be interacted with TIA1 protein through their different regions, and SKP2 and CCNA2 protein levels were positively regulated by TIA1 through suppression of mRNA decay and translational induction, respectively. These findings provide new insights into the previously unknown role of TIA1 and its isoforms as tumor-promoting molecules regulating a set of downstream oncogenic proteins, and implicate their potential application as a useful marker of malignant potential and a therapeutic target in ESCC.
Project description:Preoperative prediction of lymph node (LN) metastasis is accepted as an important independent risk factor for treatment decision-making for esophageal squamous cell carcinoma (ESCC) patients. This study aimed to develop a non-invasive biomarker to identify LN metastasis preoperatively in ESCC patients with serum exosomal RNA-seq.
Project description:This study was designed to identify genes aberrantly expressed in esophageal squamous cell carcinoma (ESCC) cells. Three esophageal squamous cell carcinoma-derived cell lines and one normal human esophageal squamous cell line were analyzed.
Project description:To understand the difference of protein expression between paired esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues, we collected 10 paired ESCC and normal tissues from surgical resected specimems for high-throughput proteomic experiments. From comparative analysis, the dysregulated signaling pathways in ESCC could be uncovered.
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 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:The purpose of this study is to explore the circRNAs expression profiles in the plasma from esophageal squamous cell carcinoma (ESCC) patients.The purpose of this study is to explore the circRNAs expression profiles in the plasma from esophageal squamous cell carcinoma (ESCC) patients.
Project description:CCAAT enhancer binding proteins (CEBPs) have critical roles in the physiological and pathological processes. However, the characteristics and contributions of CEBPs in esophageal squamous cell carcinoma (ESCC) is unknown. Here, we showed that most of CEBPs (including CEBPA, CEBPB, CEBPE, CEBPG, CEBPZ) were upregulated and amplified in ESCC. Of note, high CEBPG expression is a prognostic factor for the poor survival of patients with ESCC. Moreover, the ESCC specific transcription factor TP63 activates the expression of CEBPG by directly binding to its distal enhancer. Functionally, CEBPG significantly enhances the proliferation and migration of ESCC cells in vitro and in vivo. Mechanistically, CEBPG enhances the PI3K-AKT signaling pathways through directly binding to distal enhancer or/and promoter of downstream target genes, such as CCND1, MYC and CDK2 etc. These findings provide important characteristics and contributions insights into CEBPs dysregulation in ESCC and elucidate a crucial role for CEBPG in the progression of ESCC, which highlights its potential therapeutic target for patients.