ABSTRACT
Colorectal cancer (CRC) is the most common human digestive malignancy with a poor prognosis; the pathophysiology of colon cancer involves multiple linkages of regulatory networks. Recently, thrombospondin 2 (THBS2) has been extensively studied for its role in cancer progression. In this study, we evaluated the expression of THBS2 in CRC tissues and studied the possible mechanism by which THBS2 regulates CRC progression. Our results showed that the upregulation of THBS2 in CRC tissues and CRC cell lines and high expression of THBS2 was correlated with poor overall survival. The in vitro experimental data showed that THBS2 overexpression promoted CRC cell growth, invasion, and migration, while THBS2 inhibition exerted tumor-suppressive actions on CRC cells. THBS2 knockdown suppressed the activity of Wnt/ß-catenin signaling. Collectively, the results implied that THBS2 exerted promotional effects on CRC cell proliferation, invasion, and migration, partly by modulating the Wnt/ß-catenin signaling pathway.
Subject(s)
Colorectal Neoplasms , Thrombospondins , Wnt Signaling Pathway , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Humans , Thrombospondins/genetics , Wnt Signaling Pathway/genetics , beta Catenin/genetics , beta Catenin/metabolismABSTRACT
Background: TRIM37 has been reported to be associated with the tumorigenesis of cancers. However, the role of TRIM37 in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. This study aimed to characterize the effect of TRIM37 on T-ALL. Methods: TRIM37 expression in T-ALL patients and T-ALL cell lines was determined by qRT-PCR and Western blot. Knockdown or overexpression of TRIM37 was conducted by transferring small-interfering TRIM37 or lentivirus-mediated transducing into T-ALL cells. CCK-8 assay and flow cytometry assay were conducted to analyze the proliferation and apoptosis of T-ALL cells. Co-immunoprecipitation experiments were conducted to investigate the relationship between TRIM37 and PTEN and the ubiquitination of PTEN. Results: Our results suggested that TRIM37 expression was upregulated in the blood of T-ALL patients and T-ALL cell lines. Knockdown of TRIM37 noticeably inhibited the proliferation and promoted apoptosis of T-ALL cells. Ectopic expression of TRIM37 promoted the proliferation and suppressed the apoptosis rate of MOLT-4 cells and enhanced the phosphorylation of AKT. Moreover, TRIM37 interacted with PTEN and accelerated the degradation of PTEN via TRIM37-mediated ubiquitination in T-ALL cells. Moreover, TRIM37 reduced the sensitivity of T-ALL cells to bortezomib treatment. Additionally, PI3K/AKT signaling pathway was involved in the function of TRIM37 in T-ALL. TRIM37 contributed to the proliferation of T-ALL cells and reduced the susceptibility of T-ALL cells to bortezomib treatment through ubiquitination of PTEN and activating PI3K/AKT signaling pathway. Conclusions: Our study suggested that TRIM37 could be considered as a therapeutic target for T-ALL.
ABSTRACT
More than 40 000 patients worldwide die from esophageal cancer annually. The 5-year survival rate of patients is only ~ 15-20%, and thus, there is an ongoing need to improve diagnosis and treatment of esophageal cancer. Breast cancer type 1 susceptibility protein (BRCA1)-associated protein (BAP1) is a marker of poor prognosis in several cancers, including uveal melanoma, renal cell carcinoma, cholangiocarcinoma, non-small cell lung cancer, and colorectal cancer. BAP1 mutations are early and rare events in esophageal carcinoma, but the involvement of BAP1 in progression of esophageal carcinoma is unclear. Here, we report that cell proliferation and migration were significantly enhanced in esophageal carcinoma ECA109 cells overexpressing BAP1, while they were diminished upon BAP1 knockdown. In addition, the expression of Krüppel-like factor 5 (KLF5), CyclinD1, and FGF-BP1 was increased by BAP1 overexpression and decreased by BAP1 knockdown. Our data suggest that BAP1 promotes cell proliferation and migration, and enhances the expression of KLF5 and its downstream genes, including CyclinD1 and FGF-BP1, in the esophageal carcinoma cell line ECA109.
Subject(s)
Esophageal Neoplasms/metabolism , Tumor Suppressor Proteins/metabolism , Ubiquitin Thiolesterase/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cyclin D1/genetics , Cyclin D1/metabolism , Gene Expression/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Prognosis , Transcription Factors , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/geneticsABSTRACT
OBJECTIVE: We investigated the expression patterns, potential functions, unique prognostic value, and potential therapeutic targets of E2Fs in brain and CNS cancer and tumor-infiltrating immune cell microenvironments. METHODS: We analyzed E2F mRNA expression levels in diverse cancer types via Oncomine and GEPIA databases, respectively. Moreover, we evaluated the prognostic values using GEPIA database and TCGAportal database and the correlation of E2F expression with immune infiltration and the correlation between immune cell infiltration and GBM and LGG prognosis via TIMER database. Then, cBioPortal, GeneMANIA, and DAVID databases were used for mutation analysis, PPI network analysis of coexpressed gene, and functional enrichment analysis. RESULTS: E2F1-8 expression increased in most cancers, including brain and CNS cancer. Higher expression in E2F1, 2, 4, 6, 7, and 8 indicated poor OS of LGG. Higher E2F3-6 and E2F1-8 expressions correlated with poor prognosis and increased immune infiltration levels in CD8+ T cells, macrophages, neutrophils, and DCs in GBM and CD8+ T cells, B cells, CD4+ T cells, neutrophils, macrophages, and DCs in LGG, respectively. CONCLUSION: E2F1-8 and E2F2-8 could be hopeful prognostic biomarkers of GBM and LGG, respectively. E2F3-6 and E2F1-8 could be likely therapeutic targets in patients with immune cell infiltration of GBM and LGG, respectively.
Subject(s)
Brain Neoplasms/metabolism , Central Nervous System Neoplasms/metabolism , E2F Transcription Factors/metabolism , Biomarkers, Tumor , Brain/metabolism , Brain Neoplasms/diagnosis , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/cytology , Cell Cycle , Central Nervous System Neoplasms/diagnosis , Computational Biology/methods , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genome, Human , Genotype , Humans , Immune System , Kaplan-Meier Estimate , Macrophages/metabolism , Prognosis , Protein Interaction Mapping , RNA-Seq , Signal Transduction , Tumor MicroenvironmentABSTRACT
In present study, we purified a polysaccharide, TFPB1, from the flower buds of Tussilago farfara using DEAE-cellulose 52 anion-exchange and Sephacryl S-300 HR gel filtration chromatography. TFPB1 was a homogeneous polysaccharide with a molecular weight of 37.8kDa and composed of rhamnose, galacturonic acid, glucose, galactose, and arabinose, in a ratio of 13:13:1:7:12. Methylation and NMR results demonstrated that TFPB1 contained a rhamnogalacturonan I backbone consisting of a repeat disaccharide unit â4)-α-D-GalAp-(1â2)-α-L-Rhap-(1â, substituted by various type II arabinogalactan branches including terminal galactose, (1â3)-ß-D-galactan and (1â5)-α-L-arabinan, attached to the O-4 of (1â2)-α-L-Rhap. TFPB1 was found to inhibit cell proliferation of A549 cells and induce cell apoptosis in vitro. Furthermore, TFPB1 downregulated the phosphorylation of Akt, and upregulated caspase-3, Fas, FasL, and Bax expression, but downregulated Bcl-2 expression. Therefore, TFPB1 exhibited anti-proliferative and anti-apoptotic effect partly depending on the suppression of Akt signaling pathway. These findings provided us a potential chemotherapeutic strategy for the treatment of human non-small cell lung cancer.
