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1.
Pathol Res Pract ; 260: 155454, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39002434

RESUMO

Breast cancer (BC) is a major public health problem that affects women worldwide. Growing evidence has highlighted the role of miRNA-206 in BC pathogenesis. Changes in its expression have diagnostic and prognostic potential as they are associated with clinicopathological parameters, including lymph node metastasis, overall survival, tumor size, metastatic stage, resistance to chemotherapy, and recurrence. In the present study, we summarized, assessed, and discussed the most recent understanding of the functions of miRNA-206 in BC. Unexpectedly, miRNA-206 was found to control both oncogenic and tumor-suppressive pathways. We also considered corresponding downstream effects and upstream regulators. Finally, we addressed the diagnostic and prognostic value of miRNA-206 and its potential for the development of new therapeutic strategies.

2.
Iran J Kidney Dis ; 18(3): 179-186, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38904338

RESUMO

INTRODUCTION: Diabetic nephropathy is one of the most common severe symptoms of diabetes mellitus. Hyperglycemia can lead to tissue damage and inflammation due to mediators such as receptor for advanced glycation end-products (RAGE). Therefore, in this study, we aimed to investigate the association between the G82S polymorphism of the RAGE gene and diabetic nephropathy in diabetic patients. METHODS: In this case-control study, 356 participants (158 men and 198 women) of Asian race, aged 45 to 65 years, who were diagnosed with type 2 diabetes mellitus based on their fasting plasma glucose levels were enrolled. DNA was isolated from the participants' blood samples and genotyped using TETRA -Primer ARMS-PCR. Serum protein concentration of soluble RAGE (sRAGE) was also determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Although we found differences in genotyping of participants between homozygous AA and GG and heterozygous GA in the studied groups, the differences were not significant (P = .568). In addition, we found no significant correlation between the G82S polymorphism of RAGE and the development of diabetic nephropathy. Serum levels of sRAGE were only slightly decreased in patients with diabetic nephropathy compared with diabetic patients (P > .05). CONCLUSION: The results of this study indicate no significant association between the G82S polymorphism in the gene RAGE and the development of diabetic nephropathy. Serum levels of sRAGE were only slightly decreased in patients with diabetic nephropathy compared to diabetic patients without nephropathy. Therefore, the study suggests that there is probably no association between the G82S polymorphism in the gene RAGE and the development of diabetic nephropathy. DOI: 10.52547/ijkd.7872.


Assuntos
Povo Asiático , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Receptor para Produtos Finais de Glicação Avançada , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povo Asiático/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/sangue , Predisposição Genética para Doença , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/sangue
3.
J Recept Signal Transduct Res ; 43(4): 102-108, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38082480

RESUMO

Autophagy is a dynamic intracellular process of protein degradation, which is mostly triggered by nutrient deprivation. This process initiates with the formation of autophagosomes, which they capture cytosolic material that is then degraded upon fusion with the lysosome. Several factors have been found to be associated with autophagy modulation, of which extracellular matrix (ECM) components has attracted the attention of recent studies. Osteopontin (OPN) is an important extracellular matrix component that has been detected in a wide range of tumor cells, and is involved in cancer cell invasion and metastasis. Recently, a number of studies have focused on the relationship of OPN with autophagy, by delineating the intracellular signaling pathways that connect OPN to the autophagy process. We will summarize signaling pathways and cell surface receptors, through which OPN regulates the process of autophagy.


Assuntos
Neoplasias , Osteopontina , Humanos , Osteopontina/genética , Osteopontina/metabolismo , Transdução de Sinais/genética , Neoplasias/genética , Neoplasias/metabolismo , Autofagia/genética
5.
Sci Rep ; 12(1): 9488, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676319

RESUMO

This study is aimed to unravel the status of local and circulating ß-catenin in different primary bone tumors and its relevance to tumor types, severity, and chemotherapy. The ß-catenin mRNA expression level and the expression of the protein (intensity level) were evaluated in tumor tissue and peripheral blood mononuclear cells of 150 patients with different types of primary bone tumors (78 malignant and 72 benign tumors) using Real-Time PCR and immunohistochemistry. The ß-catenin mRNA expression level and the expression of the protein were increased in bone tumors which was positively correlated with the tumor malignancy. Amongst osteosarcoma, Ewing's Sarcoma, chondrosarcoma, osteochondroma, Giant Cell Tumor, and exostosis tumors, the osteosarcoma, and Giant Cell Tumor groups showed the highest level of ß-catenin expression. The ß-catenin expression in malignant bone tumors was significantly correlated with tumor grade, size, metastasis, tumor recurrent, and the level of response to chemotherapy. A similar pattern of ß-catenin gene expression and its association with tumor characteristics was detected in the patient's peripheral blood cells. The simultaneous increase in the expression of the ß-catenin gene and protein in tumor tissue and in circulating blood cells and its relationship with tumor severity indicates the possible promoting role of ß-catenin in primary bone tumor pathogenesis.


Assuntos
Neoplasias Ósseas , Tumores de Células Gigantes , Osteocondroma , Osteossarcoma , beta Catenina , Neoplasias Ósseas/patologia , Tumores de Células Gigantes/patologia , Humanos , Leucócitos Mononucleares/metabolismo , Osteocondroma/patologia , Osteossarcoma/patologia , RNA Mensageiro , beta Catenina/genética
6.
BMC Complement Med Ther ; 22(1): 145, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606804

RESUMO

BACKGROUND: Use of natural products has been proposed as an efficient method in modulation of immune system and treatment of cancers. The aim of this study was to investigate the potential of cryptotanshinone (CPT), naringenin, and their combination in modulating the immune response towards Th1 cells and the involvement of JAK2/STAT3 signaling pathway in these effects. METHODS: Mouse models of delayed type hypersensitivity (DTH) were produced and treated with naringenin and CPT. The proliferation of spleen cells were assessed by Bromodeoxyuridine (BrdU) assay. Flowcytometry and enzyme-linked immunosorbent assay (ELISA) tests were employed to evaluate subpopulation of T-lymphocytes and the levels of cytokines, respectively. The JAK/STAT signaling pathway was analyzed by Western blotting. RESULTS: We showed higher DTH, increased lymphocyte proliferation, decreased tumor growth and reduced JAK2/STAT3 phosphorylation in mice treated with naringenin and CPT. Moreover, a significant decline in the production of IL-4 and an upsurge in the production of IFN-γ by splenocytes were observed. Additionally, the population of intra-tumor CD4+CD25+Foxp3+ T cells was significantly lower in naringenin + CPT treated animals than that in controls. CONCLUSION: Naringenin-CPT combination could exert immunomodulatory effects, suggesting this combination as a novel complementary therapeutic regimen for breast cancer.


Assuntos
Neoplasias , Linfócitos T Reguladores , Animais , Flavanonas , Ativação Linfocitária , Camundongos , Fenantrenos
7.
ACS Appl Bio Mater ; 5(3): 1305-1318, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35201760

RESUMO

Cancer is a deadly disease that has long plagued humans and has become more prevalent in recent years. The common treatment modalities for this disease have always faced many problems and complications, and this has led to the discovery of strategies for cancer diagnosis and treatment. The use of magnetic nanoparticles in the past two decades has had a significant impact on this. One of the objectives of the present study is to introduce the special properties of these nanoparticles and how they are structured to load and transport drugs to tumors. In this study, iron oxide (Fe3O4) nanoparticles with 6 nm sizes were coated with hyperbranched polyglycerol (HPG) and folic acid (FA). The functionalized nanoparticles (10-20 nm) were less likely to aggregate compared to non-functionalized nanoparticles. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles were compared in drug loading procedures with curcumin. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles' maximal drug-loading capacities were determined to be 82 and 88%, respectively. HeLa cells and mouse L929 fibroblasts treated with nanoparticles took up more FA@HPG@Fe3O4 nanoparticles than HPG@Fe3O4 nanoparticles. The FA@HPG@Fe3O4 nanoparticles produced in the current investigation have potential as anticancer drug delivery systems. For the purpose of diagnosis, incubation of HeLa cells with nanoparticles decreased MRI signal enhancement's percentage and the largest alteration was observed after incubation with FA@HPG@Fe3O4 nanoparticles.


Assuntos
Curcumina , Neoplasias do Colo do Útero , Animais , Curcumina/farmacologia , Feminino , Ácido Fólico , Células HeLa , Humanos , Nanopartículas Magnéticas de Óxido de Ferro , Camundongos , Neoplasias do Colo do Útero/tratamento farmacológico
8.
DNA Cell Biol ; 40(7): 1026-1036, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34101492

RESUMO

NAD is mainly biosynthesized by the enzymatic action of nicotinamide phosphoribosyltransferase (NAMPT) through the salvage pathway. NAD is indispensable for the proper function and metabolism of all living cells, including cancer cells. Our previous researches revealed that inhibition of NAMPT by miRNA (miR) could suppress NAD levels and thereby hinder the growth and promotion of breast cancer (BC). Therefore, the current study was undertaken to investigate the inhibitory effects of miR-613 on NAMPT and BC cells' survival. Bioinformatics analysis and luciferase reporter assay confirmed that NAMPT 3'-untranslated region is a direct target for miR-613. The expression of miR-613 was noticed to be significantly decreased in both clinical tissue samples and BC cells by real-time PCR. Following transfection with miR-613 mimic, the expression of miR-613 was elevated in the BC cells leading to inhibition of NAMPT expression at both mRNA and protein level as measured by real-time PCR and western blotting, respectively. Inhibition of NAMPT led to a remarkable reduction in the concentration of NAD in the BC cells. The transfection also declined cell viability roughly 40% in MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Consistently, the apoptosis rate was remarkably increased, around 65% in these cells as assayed by labeling the cells with Annexin V-fluorescein isothiocyanate (FITC) and Propidium Iodide. Targeting the NAMPT-mediated NAD salvage pathway by miR-613 is a novel approach for managing BC, which is worth further investigation.


Assuntos
Neoplasias da Mama/metabolismo , Citocinas/genética , MicroRNAs/genética , Nicotinamida Fosforribosiltransferase/genética , Adulto , Apoptose/genética , Neoplasias da Mama/genética , Morte Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Citocinas/metabolismo , Feminino , Humanos , Irã (Geográfico) , MicroRNAs/metabolismo , Pessoa de Meia-Idade , NAD/genética , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo
9.
J Bone Oncol ; 23: 100300, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32551218

RESUMO

PURPOSE: The status of the local and circulating SOX9, a master regulator of the tumor fate, and its relevance to tumor types, severity, invasion feature, response to therapy, and chemotherapy treatment were surveyed in bone cancer in the current study. METHODS: The SOX9 expression level was evaluated in tissue and peripheral blood mononuclear cells from patients with different types of malignant and benign bone tumors also tumor margin tissues using Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry and western blot analysis. Also, the correlations of the SOX9 expression level with the patient's clinical and pathological features were considered. RESULTS: The remarkable overexpression of SOX9 was detected in bone tumors compared to tumor margin tissues (P < 0.0001). Malignant bone tumors revealed a higher expression of SOX9 compared to benign tumors (P < 0.0001) while osteosarcoma tumors showed higher expression levels compared to Ewing sarcoma, and chondrosarcoma. Overexpression of SOX9 was observed in high grade, metastatic, recurrent tumors also tumors with poor response to therapy. Besides, the patients under the chemotherapy treatment demonstrated higher levels of SOX9 compared to the rest of malignant tumors (P = 0.02). The simultaneous up-regulation of circulating SOX9 in the patients with bone cancer was observed compared to healthy individuals (P < 0.0001) accompanying with overexpression of SOX9 in malignant tumors compared to benign tumors (P < 0.0001). The circulating SOX9 expression was up-regulated in the patients with malignant bone tumors who receive chemotherapy treatment also patients with high grade, metastatic, recurrent tumors. The protein level of SOX9 was in line with our data on the SOX9 gene expression. CONCLUSION: The simultaneous overexpression of local and circulating SOX9 in bone cancer besides its positive correlation with tumor severity, malignancy, size, and chemotherapy may deserve receiving more attention in bone cancer diagnosis and therapy.

10.
J Cell Physiol ; 235(2): 880-890, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31256424

RESUMO

Sirtuin1 (SIRT1) is a crucial regulator of metabolism and it is implicated in the metabolic pathophysiology of several disorders inclusive of Type 2 diabetes and fatty liver disease (NAFLD). The aim of this study was to investigate the role of miR-141 in hepatic steatosis via regulation of SIRT1/AMP-activated protein kinase (AMPK) pathway in hepatocytes. Liver hepatocellular cells (HepG2) were treated with high concentration of glucose to be subsequently used for the assessment of miR-141 and SIRT1 levels in a model of hepatic steatosis. On the other hand, cells were transfected with miR-141 to investigate its effect on hepatocyte steatosis and viability as well as SIRT1 expression and activity along with AMPK phosphorylation. Targeting of SIRT1 by miR-141 was evaluated by bioinformatics tools and confirmed by luciferase reporter assay. Following the intracellular accumulation of lipids in HepG2 cells, the level of miR-141 was increased while SIRT1 mRNA and protein levels, as well as AMPK phosphorylation, was decreased. Transfection with miR-141 mimic significantly downregulated SIRT1 expression and activity while miR-141 inhibitor had the opposite effects. Additionally, modulation of miR-141 levels significantly influenced AMPK phosphorylation status. The results of luciferase reporter assay verified SIRT1 to be directly targeted by miR-141. miR-141 could effectively suppress SIRT1 and lead to decreased AMPK phosphorylation in HepG2 cells. Thus, miR-141/SIRT1/AMPK signaling pathway may be considered a potential target for the therapeutic management of NAFLD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Sirtuína 1/metabolismo , Linhagem Celular Tumoral , Células HEK293 , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Lipídeos/análise , Fígado/patologia , Obesidade/patologia
11.
BMC Cancer ; 19(1): 1027, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675930

RESUMO

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) enzyme acts as the major enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis salvage pathway. Deregulation of NAD could be associated with progression of several cancers such as breast cancer. Here, the consequence of NAMPT inhibition by miR-154 was investigated on breast cancer cells. METHODS: MDA-MB-231 and MCF-7 cancer cell lines were transfected with the mimic and inhibitors of miR-154-5p and their corresponding negative controls. Consequently, levels of NAMPT and NAD were assayed employing qRT-PCR, Western blotting and enzymatic method, respectively. Subsequently, flow cytometry and colorimetric methods were performed to evaluate apoptosis and cell viability. Bioinformatics analyses as well as luciferase assay were done to investigate whether the 3'-UTR of NAMPT is directly targeted by miR-154. RESULTS: According to the obtained results, NAMPT was recognized as a target for binding of miR-154 and the levels of this miRNA was inversely associated with both mRNA and protein levels of NAMPT in breast cancer cell lines. Functionally, miR-154 inhibited the NAD salvage pathway leading to a remarkable decrease in cell viability and increased rate of cell death. When breast cancer cells were simultaneously treated with doxorubicin and miR-154 mimic, cell viability was considerably reduced compared to treatment with doxorubicin alone in both cell lines. CONCLUSIONS: It was concluded that the inhibition of NAD production by miR-154 might be introduced as an appropriate therapeutic approach in order to improve breast cancer outcome either alone or in combination with other conventional chemotherapeutic agents.


Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Regiões 3' não Traduzidas/genética , Antineoplásicos Alquilantes/uso terapêutico , Apoptose , Neoplasias da Mama/tratamento farmacológico , Sobrevivência Celular , Biologia Computacional , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Ativação Enzimática/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Nicotinamida Fosforribosiltransferase/genética
12.
EXCLI J ; 18: 683-696, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611752

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme involved in nicotinamide adenine dinucleotide (NAD) salvage pathway, is overexpressed in many human malignancies such as breast cancer. This enzyme plays a critical role in survival and growth of cancer cells. MicroRNAs (miRNAs) are among the most important regulators of gene expression, and serve as potential targets for diagnosis, prognosis, and therapy of breast cancer. Therefore, the aim of this study was to assess the effect of NAMPT inhibition by miR-381 on breast cancer cell survival. MCF-7 and MDA-MB-231 cancer cell lines were transfected with miR-381 mimic, inhibitor, and their corresponding negative controls (NCs). Subsequently, the level of NAMPT and NAD was assessed using real-time PCR, immuno-blotting, and enzymatic methods, respectively. In order to evaluate apoptosis, cells were labelled with Annexin V-FITC and propidium iodide and analyzed by flow cytometry. Bioinformatics analysis was performed to recognize whether NAMPT 3'-untranslated region (UTR) is a direct target of miR-381 and the results were authenticated by the luciferase reporter assay using a vector containing the 3'-UTR sequence of NAMPT. Our results revealed that the 3'-UTR of NAMPT was a direct target of miR-381 and its up-regulation decreased NAMPT gene and protein expression, leading to a notable reduction in intracellular NAD and subsequently cell survival and induction of apoptosis. It can be concluded that miR-381 has a vital role in tumor suppression by down-regulation of NAMPT, and it can be a promising candidate for breast cancer therapy.

13.
EXCLI J ; 18: 838-851, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645844

RESUMO

Breast cancer (BC) is the most prevalent cause of cancer-related death in women worldwide. BC is frequently associated with elevated levels of nicotinamide phosphoribosyltransferase (NAMPT) in blood and tumor tissue. MicroRNA-494 (miR-494) has been described to play key anti-tumor roles in human cancers. The aim of the present study was to investigate the inhibitory effect of miR-494 on NAMPT-mediated viability of BC cells. In this experimental study, MCF-7 and MDA-MB-231 cells were cultured and then transfected with miR-494 mimic, miR-494 inhibitor and their negative controls. The mRNA and protein expression of NAMPT were assessed using real-time PCR and Western blotting, respectively. Subsequently, intracellular NAD levels were determined by a colorimetric method. Finally, cell apoptosis was examined by flow cytometry. Bioinformatics evaluations predicted NAMPT as a miR-494 target gene which was confirmed by luciferase reporter assay. Our results showed an inverse relationship between the expression of miR-494 and NAMPT in both MCF-7 and MDA-MB-231 cell lines. miR-494 significantly down-regulated NAMPT mRNA and protein expression and was also able to reduce the cellular NAD content. Cell viability was decreased following miR-494 up-regulation. In addition, apoptosis was induced in MCF-7 and MDA-MB-231 cells by miR-494 mimic. Our findings indicate that miR-494 acts as a tumor suppressor and has an important effect in suppressing the growth of BC cells through NAMPT. Therefore, miR-494 might be considered as a novel therapeutic target for the management of human breast cancer.

14.
Gene ; 711: 143939, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31220581

RESUMO

Sirtuin 1 is one of the regulators of cell growth and survival and its inhibition is suggested as a suitable mechanism to overcome breast cancer development. In this study we explored the role of miR-211-5p in SIRT1/p53 pathway and its influence on breast cancer cell viability and apoptosis. Cells were transfected with miR-211-5p mimic and inhibitor to modulate cellular miR-211-5p levels in breast cancer cell lines, MDA-MB-231 and MCF-7. Gene expression of miR-211-5p and SIRT1 were measured with real-time PCR. SIRT1 protein level and the acetylation of p53 as well as SIRT1 activity were evaluated by Western blotting and fluorometry, respectively. In order to explore the direct attachment of miR-211-5p to the 3'-UTR of SIRT1 mRNA, luciferase reporter assay was applied. Cell viability in response to miR-211-5p was studied by MTT assay and apoptosis was assessed by annexin V labeling followed by flow cytometry. Results showed that SIRT1 gene and protein expression were inhibited by miR-211-5p and the 3'-UTR of SIRT1 was found to be directly targeted by miR-211-5p. Inhibition of SIRT1 expression resulted in its reduced activity. Up-regulation of miR-211-5p was also followed by a significant decline in the acetylation status of p53 which was associated with remarkable decreased cell viability and induction of apoptosis in breast cancer cells. Antisense oligonucleotide of miR-211-5p acted as its inhibitor and exerted opposite effects both on SIRT1 expression and cell apoptosis. In conclusion, inhibition of SIRT1 by miR-211-5p could effectively reduce breast cancer cell survival and cause cell death and therefore might be considered a seemly mechanism for designing anticancer therapies.


Assuntos
Neoplasias da Mama/metabolismo , MicroRNAs/genética , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Regiões 3' não Traduzidas , Acetilação , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7
15.
Biochem Genet ; 57(4): 507-521, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30697640

RESUMO

Non-alcoholic fatty liver disease is one of the main causes of chronic liver disease and therefore is currently considered a major public health problem. Sirtuin 1 (SIRT1) is an NAD-dependent deacetylase enzyme that contributes in the regulation of metabolic processes and protects against lipid accumulation in hepatocytes. Its expression is potentially regulated by microRNAs which attach to the 3' untranslated region (3'-UTR) of their target mRNA. HepG2 cells were incubated by glucose to induce lipid accumulation and were subsequently transfected with mir-23b mimic and inhibitor. Real-time PCR was used for measuring the expression of mir-23b and SIRT1 mRNA. Cell survival assay and intracellular triglyceride measurement were performed using colorimetric methods. Determination of SIRT1 protein level and activity were done by western blot and fluorometric analysis, respectively. The interaction of miR-23b with 3'-UTR of SIRT1 mRNA was confirmed by dual luciferase. miR-23b mimic inhibited gene and protein expression of SIRT1, while the inhibitor of miR-23b significantly elevated the expression levels of SIRT1 mRNA and protein. The results showed that the 3'-UTR of SIRT1 mRNA is a direct target for miR-23b. The intracellular triglyceride level was increased following the inhibition of SIRT1 in transfected HepG2 cell by miR-23b mimic. Cell viability was decreased in response to miR-23b upregulation compared to control cells. miR-23b reduces the expression and activity of SIRT1 and therefore may be a causative factor in the enhancement of lipid accumulation in HepG2 cells.


Assuntos
Hepatócitos/metabolismo , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/genética , Regiões 3' não Traduzidas , Sobrevivência Celular/genética , Regulação para Baixo , Células HEK293 , Células Hep G2 , Humanos , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sirtuína 1/metabolismo , Triglicerídeos/metabolismo , Regulação para Cima
16.
J Cell Biochem ; 120(6): 9356-9368, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30520099

RESUMO

Downregulation of microRNA-590-3p (miR-590-3p) is a frequently occurring, nonphysiological event which is observed in several human cancers, especially breast cancer. However, the significance of miR-590-3p still remain unclear in the progression of this disease. This study explored the role of miR-590-3p in apoptosis of breast cancer cells. Gene expression of miR-590-3p, Sirtuin-1 (SIRT1), Bcl-2 associated X protein (BAX), and p21 was evaluated with real-time polymerase chain reaction (PCR) and SIRT1 protein expression was assessed by Western blot analysis in breast cancer cell lines. Bioinformatics analysis and luciferase reporter assay were used to evaluate targeting of SIRT1 messenger RNA (mRNA) by miR-590-3p. Cells were transfected with miR-590-3p mimic and inhibitor and their effects on the expression and activity of SIRT1 were evaluated. The effects of miR-590-3p upregulation on the acetylation of p53 as well as cell viability and apoptosis were assessed by Western blot analysis, WST-1 assay, and flow cytometry, respectively. miR-590-3p expression was considerably downregulated in breast cancer cells which was accompanied by upregulation of SIRT1 expression. SIRT1 was recognized as a direct target for miR-590-3p in breast cancer cells and its protein expression and activity was dramatically inhibited by the miR-590-3p. In addition, there was an increase in p53 and its acetylated form that ultimately led to upregulation of BAX and p21 expression, suppression of cell survival, and considerable induction of apoptosis in breast cancer cells. These findings suggest that miR-590-3p exerts tumor-suppressing effects through targeting SIRT1 in breast cancer cells, which makes it a potential therapeutic target for developing more efficient treatments for breast cancer.


Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Sirtuína 1/genética , Proteína Supressora de Tumor p53/genética , Apoptose/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Transdução de Sinais/genética
17.
Gene ; 673: 149-158, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-29886033

RESUMO

Nicotinamide adenine dinucleotide (NAD) is a critical coenzyme for all living cells. Nicotinamide phosphoribosyltransferase (NAMPT) functions as a key enzyme in the salvage pathway of NAD biosynthesis. Cancer cells have higher rate of NAD consumption and therefore NAMPT is essential for their survival. Thus, we investigated the effect of NAMPT inhibition by miR-206 on breast cancer cell survival. Breast cancer cells were transfected with miR-206 mimic, inhibitor and their negative controls. NAMPT levels were assessed by real-time PCR as well as western blotting. Cell survival assay and quantification of NAD level were performed by using colorimetric methods. Apoptosis assay was performed by labeling cells with Annexin V-FITC and propidium iodide followed by the flow cytometric analysis. Bioinformatics analysis was done to assess whether NAMPT 3'-UTR is a direct target of miR-206 and the results were confirmed by the luciferase reporter assay. NAMPT 3'-UTR was shown to be a direct target of miR-206. miR-206 reduced NAMPT expression at the protein level, leading to a significant decrease in the intracellular NAD level and subsequent decline in cell survival and induction of apoptosis. Targeting of NAMPT-mediated NAD salvage pathway by miR-206 might provide a new insight in the possible molecular mechanism of breast cancer cell growth regulation. This pathway might provide a new approach for breast cancer therapy.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Citocinas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Regiões 3' não Traduzidas , Apoptose , Western Blotting , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Luciferases/metabolismo , Células MCF-7 , MicroRNAs/genética
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