RESUMO
PAX5, a member of the Paired Box (PAX) transcription factor family, is an essential factor for B-lineage identity during lymphoid differentiation. Mechanistically, PAX5 controls gene expression profiles, which are pivotal to cellular processes such as viability, proliferation, and differentiation. Given its crucial function in B-cell development, PAX5 aberrant expression also correlates with hallmark cancer processes leading to hematological and other types of cancer lesions. Despite the well-established association of PAX5 in the development, maintenance, and progression of cancer disease, the use of PAX5 as a cancer biomarker or therapeutic target has yet to be implemented. This may be partly due to the assortment of PAX5 expressed products, which layers the complexity of their function and role in various regulatory networks and biological processes. In this review, we provide an overview of the reported data describing PAX5 products, their regulation, and function in cellular processes, cellular biology, and neoplasm.
Assuntos
Fator de Transcrição PAX5 , Proteínas , Diferenciação Celular/genética , Hematopoese , Fator de Transcrição PAX5/genética , Fator de Transcrição PAX5/metabolismoRESUMO
Metastasis is known as a key step in cancer recurrence and could be stimulated by multiple factors. Calumenin (CALU) is one of these factors which has a direct impact on cancer metastasis and yet, its underlined mechanisms have not been completely elucidated. The current study was aimed to identify CALU co-expressed genes, their signaling pathways, and expression status within the human cancers. To this point, CALU associated genes were visualized using the Cytoscape plugin BisoGenet and annotated with the Enrichr web-based application. The list of CALU related diseases was retrieved using the DisGenNet, and cancer datasets were downloaded from The Cancer Genome Atlas (TCGA) and analyzed with the Cufflink software. ROC curve analysis was used to estimate the diagnostic accuracy of DEGs in each cancer, and the Kaplan-Meier survival analysis was performed to plot the overall survival of patients. The protein level of the signature biomarkers was measured in 40 biopsy specimens and matched adjacent normal tissues collected from CRC and lung cancer patients. Analysis of CALU co-expressed genes network in TCGA datasets indicated that the network is markedly altered in human colon (COAD) and lung (LUAD) cancers. Diagnostic accuracy estimation of differentially expressed genes showed that a gene panel consisted of CALU, AURKA, and MCM2 was able to successfully distinguish cancer tumors from healthy samples. Cancer cases with abnormal expression of the signature genes had a significantly lower survival rate than other patients. Additionally, comparison of CALU, AURKA, and MCM2 proteins between healthy samples, early and advanced tumors showed that the level of these proteins was increased through normal-carcinoma transition in both types of cancers. These data indicate that the interactions between CALU, AURKA, and MCM2 has a pivotal role in cancer development, and thereby needs to be explored in the future.
Assuntos
Aurora Quinase A , Proteínas de Ligação ao Cálcio , Neoplasias do Colo , Bases de Dados de Ácidos Nucleicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Componente 2 do Complexo de Manutenção de Minicromossomo , Aurora Quinase A/biossíntese , Aurora Quinase A/genética , Proteínas de Ligação ao Cálcio/biossíntese , Proteínas de Ligação ao Cálcio/genética , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Componente 2 do Complexo de Manutenção de Minicromossomo/biossíntese , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Metástase Neoplásica , Taxa de SobrevidaRESUMO
Modulation of fatty acids metabolism is an appropriate strategy for starvation-induced death in tumor cancers. Colon cancer cells express a high level of acyl-CoA synthetase-5 (ACSL5), and as yet no therapeutic approach has been achieved. Herein, ACSL5-related microRNAs (miRNAs) were identified via TargetScan, and their impacts on ACSL5 and lipid content along with metabolic activity, cell cycle, migration, and invasion of colorectal cancer (CRC) cells were examined, and subsequently compared with transcriptome for better visualization of intracellular-signaling networks. In vivo analysis was performed using BALB/c mice xenograft model of CRC injected with target miRNA. Clinical significances were also evaluated in 80 CRC tumors and matched adjacent normal tissues. There was a reverse correlation between ACSL5 and miR-497-5p, which miR-497-5p overexpression modulated CRC cell proliferation and development. A similar observation was received from the in vivo examination in which intratumoral injection of miR-497-5p reversed the tumor growth in the CRC xenograft model. Downregulation of miR-497-5p correlated with tumor differentiation, tumor, node, and metastasis staging, lymph node metastasis, and poor survival in patients with CRC. These results suggested that miR-497-5p upregulation could be considered as a therapeutic strategy for modulation of lipid metabolism in colon cancer.
Assuntos
Proliferação de Células/genética , Coenzima A Ligases/genética , Neoplasias do Colo/genética , MicroRNAs/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Metabolismo dos Lipídeos/genética , Camundongos , Inanição/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Natural dietary ingredients like flavonoids are important for body improvement against diseases. The flavonol rutin is widely found in fruits and vegetables and shows significant anticancer properties. However, the underlined signaling pathways have not been elucidated yet. In this study, the impacts of various doses of rutin (400-700 mM/ml) have been examined on human colon cancer SW480 cells metabolism, cell cycle, and apoptosis. The transcriptome was analyzed by bioinformatics tools and the interactions between rutin modulated microRNAs (miRNAs), long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), and transcription factors (TFs) were built, filtered and enriched. A dose of 600 mM of rutin significantly decreased cells metabolic activity, halved the population and arrested the cell cycle at the sub-G1 phase. The enrichment analysis of miRNAs-lncRNAs-mRNAs-TFs network showed that these effects were mediated through alteration of glucose, lipid, and protein metabolism, modulating endoplasmic reticulum stress responses, negative regulation of cell cycle process, and inducing the extrinsic and intrinsic apoptotic signaling pathways. Additionally, the key parent nodes of each annotation were illustrated. These findings create a detailed image of rutin underlying intracellular signaling pathways in CRC and also help us to better understand the role of dietary natural compounds in cancer treatment.