CHI3L1 regulates papillary thyroid tumor progression via TP53 signaling
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ABSTRACT:
PROVIDER: PRJNA1204810 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: This study aimed to investigate the potential impacts of the CHI3L1 gene on the progression of papillary thyroid carcinoma (PTC) and to propose novel therapeutic approaches. Methods: CHI3L1 expression in PTC was analyzed using public datasets. Cell proliferation was assessed using the CCK-8 assay and colony formation assay. Tumor growth was evaluated using nude mouse xenograft models. Cell invasion was evaluated using the transwell assay, while cell migration was assessed with the wound healing assay. Transcriptomic analysis was conducted to examine the molecular mechanism, and real-time quantitative PCR was performed for gene expression validation. Results: The findings revealed that CHI3L1 expression was upregulated in various cancers, mainly in PTC. Both in vitro and in vivo assays demonstrated that cell proliferation was suppressed when CHI3L1 was knocked down. Transcriptome sequencing indicated that CHI3L1 knockdown was associated with migration-related pathways and TP53 signaling pathway. Transwell assays showed reduced cell invasion upon CHI3L1 suppression, while wound healing assays demonstrated decreased cell migration. Following CHI3L1 silencing, real-time quantitative PCR verified the overexpression of TP53-related genes. Survival analysis further indicated a correlation between elevated CHI3L1 expression and reduced survival rates. Conclusion: This study identified that CHI3L1 was an oncogene in human papillary thyroid cells and suggested that it may influence tumorigenesis through the TP53 signaling pathway. Thus, CHI3L1 could serve as a potential therapeutic target for PTC patients.
2025-01-02 | GSE285569 | GEO
Project description:Anaplastic thyroid carcinoma (ATC) has among the worst prognosis of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. BRAF and TP53 mutations co-occur in a high proportion of ATC, particularly those associated with a precursor papillary thyroid carcinoma (PTC). In order to develop an adult-onset model of BRAF-mutant anaplastic thyroid carcinoma, we generated a novel thyroid-specific CreER transgenic mouse. We utilize a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from papillary to anaplastic thyroid carcinoma. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis and rapid lethality. We employed small animal ultrasound imaging to monitor autochthonous tumors, and show that treatment with the selective BRAF inhibitor PLX4720 improved survival, but did not lead to tumor regression or suppress signaling through the MAPK pathway. Combination of PLX4720 and the MEK inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines, and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. Total RNA from five murine papillary thyroid carcinoma (PTC) tumors and five murine anaplastic thyroid carcinoma (ATC) tumors was analyzed.
2014-04-02 | E-GEOD-55933 | biostudies-arrayexpress
Project description:CHI3L1 (Chitinase-3-like protein 1), also known as YKL-40, has been associated with inflammation and cancer. Transcription profiling analysis was performed in FTC-133 thyroid cancer cells transfected with control siRNA or siRNAs against CHI3L1.
2020-02-12 | GSE145077 | GEO
Project description:Anaplastic thyroid carcinoma (ATC) has among the worst prognosis of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. BRAF and TP53 mutations co-occur in a high proportion of ATC, particularly those associated with a precursor papillary thyroid carcinoma (PTC). In order to develop an adult-onset model of BRAF-mutant anaplastic thyroid carcinoma, we generated a novel thyroid-specific CreER transgenic mouse. We utilize a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from papillary to anaplastic thyroid carcinoma. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis and rapid lethality. We employed small animal ultrasound imaging to monitor autochthonous tumors, and show that treatment with the selective BRAF inhibitor PLX4720 improved survival, but did not lead to tumor regression or suppress signaling through the MAPK pathway. Combination of PLX4720 and the MEK inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines, and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma.
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Project description:Label-free proteomics profiling of 37 paired tumor-normal tissues of papillary thyroid cancer
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Project description:We compared the expression profiles of papillary thyroid tumors from the Chernobyl Tissues Bank (CTB) with tumors from French patients with no history of exposure to radiations. Keywords: papillary thyroid cancer vs. patient-matched healthy adjacent thyroid thyroid papillary cancer vs. patient-matched adjacent nontumor thyroid tissues. -14 tumors from France -12 tumors from Ukraine
2007-07-11 | E-GEOD-3950 | biostudies-arrayexpress
Project description:Phosphorylated proteomics profiling were performed on 37 paired tumor-normal tissues of human papillary thyroid cancer
2024-02-08 | PXD045017 | Pride
Project description:The dysregulation of circular RNAs (circRNAs) has been implicated in the development and progression of papillary thyroid cancer (PTC). In this study, we analyzed the dysregulated circRNA profile using PTC tissues and matched adjacent normal tissues by RNA-seq.
2023-07-27 | GSE237841 | GEO
Project description:Mice with thyroid-specific expression of oncogenic BRAF (Tg-Braf) develop papillary thyroid cancers (PTC) that are locally invasive and have well-defined foci of poorly differentiated thyroid carcinoma (PDTC). To investigate the PTC-PDTC progression, we performed a microarray analysis using RNA from paired samples of PDTC and PTC collected from the same animals by laser capture microdissection. Analysis of 8 paired samples revealed a profound deregulation of genes involved in cell adhesion and intracellular junctions, with changes consistent with an epithelial-mesenchymal transition (EMT). This was confirmed by IHC, as vimentin expression was increased and E-cadherin lost in PDTC compared to adjacent PTC. Moreover, PDTC stained positively for phospho-Smad2, suggesting a role for transforming growth factor-beta (TGFbeta) in mediating this process. Accordingly, TGFbeta induced EMT in primary cultures of thyroid cells from Tg-Braf mice, whereas wild-type thyroid cells retained their epithelial features. TGFbeta-induced Smad2 phosphorylation, transcriptional activity and induction of EMT required MAPK pathway activation in Tg-Braf thyrocytes. Hence, tumor initiation by oncogenic BRAF renders thyroid cells susceptible to TGFbeta-induced EMT, through a MAPK-dependent process. Comparing the transcription profiles of 8 pairs of murine poorly differentiated thyroid cancer and papillary thyroid cancer collected from the same animals by laser capture microdissection. Co-hybridizations were done in triplicate with a single dye flip.
2011-03-22 | E-GEOD-27668 | biostudies-arrayexpress
Project description:We compared the expression profiles of papillary thyroid tumors from the Chernobyl Tissues Bank (CTB) with tumors from French patients with no history of exposure to radiations. Keywords: papillary thyroid cancer vs. patient-matched healthy adjacent thyroid
2007-07-12 | GSE3950 | GEO