Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Biochem Mol Toxicol ; : e22469, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32173973

RESUMO

We aimed to investigate the effects of Krüppel-like factor 5 (KLF5) on cell biological function and chemotherapy sensitivity of anaplastic thyroid carcinoma (ATC) and explore the underlying mechanism. In this study, we found that KLF5 was expressed higher in ATC cells than that in normal thyroid cells. Knockdown of KLF5 inhibited proliferation, induced apoptosis and restrained invasion and migration abilities of ATC cells. KLF5 overexpression promoted proliferation and inhibited apoptosis of ATC cells in response to doxorubicin (Dox), whereas KLF5 knockdown increased the sensitivity of ATC cells to Dox. Multidrug resistance gene 1/permeability glycoprotein and ATP-binding cassette superfamily G member 2 were heightened in ATC cells with KLF5 overexpression, but the opposite results were found in sh-KLF5-treated cells. Phosphorylation (p)-c-Jun N-terminal kinase (JNK) was upregulated in KLF5 overexpression cells, whereas it was downregulated in the KLF5 knockdown treatment group. Furthermore, KLF5 knockdown inhibited ATC growth and enhanced the Dox sensitivity of ATC by inactivating the JNK signaling pathway. Taken together, our findings concluded that KLF5 knockdown can remarkably inhibit the proliferation, invasion, and migration and induce apoptosis of ATC cells, and increase the chemotherapy sensitivity of ATC, all of which probably through inhibiting the JNK signaling pathway.

2.
Sci Rep ; 9(1): 19645, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31873123

RESUMO

The mitotic serine/threonine kinase aurora kinase-A (AURKA) has been identified as carcinogenic in hepatocellular carcinoma (HCC). AURKAPS1, a long non-coding RNA (lncRNA), is the pseudo-gene of AURKA, which play important roles in the cancer. Its underlying functions and mechanisms in liver cancer progression remain largely unknown. The mRNA expression of AURKAPS1 in HCC tumor tissues was significantly higher, which is associated with tumor size and TNM stage. The high expression of AURKAPS1 promotes cell movement, migration and invasion. AURKAPS1 can increases the protein expression of RAC1, promotes the activation of ERK, and enhance the formation of membrane ruffles by binding with miR-182, miR-155 and miR-142 competively. Thus, AURKAPS1 could be a useful marker, and the combination of AURKAPS1/miRNAs (miR-142, miR-155 and miR-182) may be a new theoretical basis for the treatment of HCC.

3.
Gastric Cancer ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673844

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly investigated in numerous carcinomas containing gastric cancer (GC). The aim of our research is to inquire about the expression profile and role of LBX2-AS1 in GC. METHODS: The expressions of LBX2-AS1, miR-219a-2-3p, FUS and LBX2 were measured by qRT-PCR. Western blot evaluated FUS and LBX2 protein levels. Cell proliferation and apoptosis were, respectively, evaluated by CCK-8, colony formation, EdU, flow cytometry and TUNEL assays. FISH and subcellular fractionation assays examined the position of LBX2-AS1. The binding between genes were certified by RIP, RNA pull-down, ChIP and luciferase reporter assays. Pearson correlation analysis analyzed the association of genes. Kaplan-Meier method detected the relationship of LBX2-AS1 expression with overall survival. RESULTS: The up-regulation of LBX2-AS1 in GC tissues and cells was verified. Function assays proved that LBX2-AS1 down-regulation restricted the proliferation ability. Then, we unveiled the LBX2-AS1/miR-219a-2-3p/FUS axis. Additionally, LBX2-AS1 positively regulated LBX2 mRNA stability via FUS. LBX2 transcriptionally modulated LBX2-AS1. In the end, rescue and in vivo experiments validated the whole regulatory mechanism. CONCLUSION: LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop mainly affected the proliferation and apoptosis abilities of GC cells, offering novel therapeutic targets for the treatment of patients with GC.

4.
Endocrine ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637658

RESUMO

PURPOSE: Several studies have reported different findings on the prognosis of differentiated thyroid carcinoma combined with Graves' disease. To assess the effect of Graves' disease on differentiated thyroid carcinoma, a meta-analysis was undertaken. METHODS: PubMed, OVID and the Cochrane Library were systematically searched for trials published prior to Oct. 2018. Studies containing data on the outcomes of Graves' disease with differentiated thyroid carcinoma were included. Summary estimates of the prevalence of recurrence/disease progression/persistence and mortality as well as odds ratios and weighted mean differences were calculated with a random-effects model. RESULTS: Of the 916 related articles found, 13 fulfilled the inclusion criteria. The recurrence/disease progression/persistent rate was not significantly different between the Graves' disease group and the non-Graves' disease group (P = 0.86). However, the analysis of three studies with K-M curves or HRs showed that there was a significant difference between the two groups (P = 0.04). Subgroup analysis showed that the contradictory results could be due to the location/race assessed in the studies. Graves' disease almost acted as a risk factor (OR = 1.77, 95%C.I. = 0.99-3.16) for differentiated thyroid carcinoma in European studies. When heterogeneous studies were excluded, the analyses show that GD was a risk factor for recurrence/disease progression/persistence (P = 0.03, OR = 1.75, 95%C.I. = 1.04-2.95). The overall mortality rate was significantly higher in the Graves' disease group than in the non-Graves' disease group (P = 0.02, OR = 2.93, 95%C.I. = 1.17-7.37). CONCLUSIONS: Graves' disease acts as a risk factor for the prognosis of differentiated thyroid carcinoma. The recurrence/disease progression/persistent rate may be affected by TSAbs in a specific location/race and with a genetic immunization background. However, the histotypes and subtypes may play an important role in mortality rate.

5.
Sci Rep ; 9(1): 5800, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967566

RESUMO

Papillary thyroid microcarcinoma accounts for a large proportion of papillary thyroid carcinoma, especially among new cases. Many  PTMC patients have regional lymph node metastasis, with some experiencing recurrence and even death. However, the risk factors and mechanism by which PTMC relates to these factors are unknown. In this study, differentially expressed genes were identified with microarray from The Cancer Genome Atlas, followed by analysis using the Kyoto Encyclopedia of Genes and Genomes. Immunohistochemistry, immunofluorescence, western blot and Oil Red O staining were carried out to evaluate expression levels and functional alterations. Mesenteric Estrogen Dependent Adipogenesis expression was observed in almost all cases of papillary thyroid microcarcinomas, and the location of expression was associated with histological subtype. High expression was correlated with metastasis and poor disease-free survival. Furthermore, the enrichment analysis indicated that Mesenteric Estrogen Dependent Adipogenesis expression may be associated with metabolic reprogramming to influence metastasis and prognosis. These findings contribute to a better understanding of how Mesenteric Estrogen Dependent Adipogenesis affects metastasis and the prognosis of papillary thyroid microcarcinoma patients and suggest that Mesenteric Estrogen Dependent Adipogenesis expression may be a novel prognostic marker in these patients.

6.
Genet Test Mol Biomarkers ; 23(3): 156-165, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30807260

RESUMO

AIMS: Increasing evidence links the abnormal expression of microRNAs and ATP-binding cassette subfamily C member 4 (ABCC4) with tumor development and progression, as well as with chemoresistance. Our aims were to determine the therapeutic potential of targeting both miR-124-3p and ABCC4 in breast cancer cells and to determine if duel targeting increased their sensitivity to chemotherapeutic drugs, in vitro. MATERIALS AND METHODS: The expression of the ABCC4 protein and miR-124-3p were detected, respectively, by immunohistochemical staining and quantitative real-time polymerase chain reaction in breast cancer tumor tissue, MCF-7 and MCF-7-ADR cell lines. Suppression of ABCC4 expression and miR-124-3p overexpression were performed in MCF-7-ADR cell lines. Western blot assays were used to detect expression of ABCC4 and permeability glycoprotein 1/multi-drug resistance protein 1 (P-gp) in cells. Cell Counting Kit-8, flow cytometry, transwell, and scratch assays were conducted to detect cell proliferation, cell cycle, invasion, and migration of cells. RESULTS: We found that ABCC4 protein expression was significantly increased, while the miR-124-3p level was significantly decreased in breast cancer tissue and cell lines. Tumor size and clinical tumor node metastasis stage were significantly correlated with elevated expression of ABCC4 and decreased expression of miR-124-3p. Interestingly, ABCC4 expression was significantly increased in MCF-7-ADR cells, while miR-124-3p level was significantly decreased compared with MCF-7 cells. The inhibition of ABCC4 and miR-124-3p overexpression both led to a significant decrease in cell proliferation, invasion, and migration of MCF-7-ADR cells, and combination of suppression of ABCC4 with miR-124-3p overexpression had a synergistic inhibitory effect. Our results further demonstrated that inhibition of ABCC4 expression and overexpression of miR-124-3p significantly enhanced the sensitivity to adriamycin (ADR) in MCF-7-ADR cells, and that simultaneous dual-targeting of miR-124-3p and ABCC4 had a stronger promotive effect on the sensitivity to ADR in MCF-7-ADR cells. Moreover, western blot analysis showed that miR-124-3p overexpression significantly inhibited P-gp expression in MCF-7-ADR cells. CONCLUSION: Our data demonstrate that the combination of downregulation of ABCC4 with overexpression of miR-124-3p significantly increased sensitivity to ADR in MCF-7-ADR cells. This finding suggests that similar dual targeting may serve as a means to enhance therapies for drug-resistant breast cancers.


Assuntos
Doxorrubicina/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Regiões 3' não Traduzidas , Adulto , Idoso , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , MicroRNAs/efeitos dos fármacos , MicroRNAs/metabolismo , MicroRNAs/fisiologia , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/fisiologia , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos
7.
J Cell Physiol ; 234(8): 14031-14039, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30628071

RESUMO

Breast cancer is a one of the most malignant threats among women worldwide. However, the mechanism underlying breast cancer development remains unclear. Long noncoding RNAs (lncRNAs) have been reported to participate in breast cancer. Whether lncRNA LINC01857 is involved in breast cancer requires investigation. In this study, we found that LINC01857 was highly expressed in breast cancer tissues and cells (p < 0.05). High LINC01857 expression predicted poor prognosis in breast cancer patients. Functionally, LINC01857 silencing impaired proliferation and enhanced apoptosis of breast cancer cells ( p < 0.05). Decreased LINC01857 inhibited breast cancer cells migration and invasion ability ( p < 0.05). In terms of mechanism, LINC01857 promoted H3K27Ac deposition on CREB1 promoter and initiated its transcription by recruiting CREBBP. Overexpression of CREB1 reversed the biological behavior of breast cancer cells induced by LINC01857 silencing ( p < 0.05). Taken together, our findings demonstrated that LINC01857 promoted breast cancer development by promoting H3K27Ac and CREB1 transcription via enhancing CREBBP enrichment in the CREB1 promoter region.

8.
Biomed Pharmacother ; 110: 294-301, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30522015

RESUMO

The long non-coding RNA (lncRNA) has recently been shown to be important regulators involved in the progression of various human cancers. Small nucleolar RNA host gene 6 (SNHG6) is a recently identified cancer-related lncRNA. However, the clinical significance and biological function of SNHG6 in breast cancer (BC) are still unclear. In the present study, we found that SNHG6 was highly expressed in BC tissues and cell lines, which was associated with poorer clinicopathologic features. Knockdown of SNHG6 inhibited BC cell proliferation, migration and invasion in vitro and in vivo using CCK-8, Edu staining, transwell assays and nude mice model. Moreover, bioinformatics analysis and luciferase reporter experiments indicated that SNHG6 serves as an endogenous sponge by directly binding to miR-26a-5p and down-regulating miR-26a-5p expression. MiR-26a-5p overexpression significantly enhanced the effect of SNHG6 knockdown on the cell behaviors in BC. Furthermore, bioinformatics analysis and luciferase reporter indicated that MAPK6 was validated as a target of miR-26a-5p. Therefore, our study may reveal a novel SNHG6/miR-26a-5p/MAPK6 pathway regulatory axis in BC pathogenesis. SNHG6 may serve as a potential prognostic and therapeutic target in the treatment of BC.


Assuntos
Neoplasias da Mama/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , MicroRNAs/biossíntese , Proteína Quinase 6 Ativada por Mitógeno/biossíntese , RNA Longo não Codificante/biossíntese , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Proteína Quinase 6 Ativada por Mitógeno/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Longo não Codificante/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
9.
Arch Biochem Biophys ; 661: 22-30, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30389444

RESUMO

Increasing studies have highlighted the critical role of lncRNAs in cancer pathogenesis and development. LncRNA maternally expressed gene 3 (MEG3) was reported to function as a tumor suppressor in breast cancer. However, the detailed molecular mechanism of MEG3 involved in breast cancer progression remains far from being addressed. Our findings showed that MEG3 was downregulated and miR-21 was upregulated in breast cancer patient tissues and cells. MEG3 overexpression suppressed cell proliferation and glycolysis, and induced apoptosis in breast cancer cells. MEG3 was demonstrated to function as a molecular sponge of miR-21 and suppress its expression. Moreover, miR-21 upregulation partially abolished the effects of MEG3 overexpression on cell proliferation, glycolysis, and apoptosis in breast cancer cells. Additionally, enforced expression of MEG3 reversed miR-21-mediated activation of PI3K/Akt pathway in breast cancer cells. In vivo experiment demonstrated that overexpression of MEG3 inhibited tumor growth in breast cancer by suppressing miR-21. In summary, MEG3 overexpression inhibited the tumorigenesis of breast cancer by downregulating miR-21 through the PI3K/Akt pathway.


Assuntos
Neoplasias da Mama/metabolismo , Carcinogênese/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , MicroRNAs/biossíntese , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Proliferação de Células/genética , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Transdução de Sinais
10.
Biol Chem ; 400(5): 639-650, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30391932

RESUMO

This study aims to investigate the mechanism of miR-23a-3p in regulating Treg dysfunction in Graves' disease (GD). The percentage of Treg cells and interleukin (IL)-17+ T cells were determined by flow cytometry. The expression of forkhead box P3 (FOXP3), sirtuin 1 (SIRT1), RAR-related orphan receptor gamma t (RORγt) and miR-23a-3p was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blot. CD4+ T cells were treated with SIRT1 specific inhibitor EX-527 or left untreated. MiR-23a-3p mimic or inhibitor were transfected into CD4+ T cells. Acetylation expression of FOXP3 was analyzed by immunoprecipitation. The suppressive function of Treg was analyzed by the carboxyfluorescein succinimidyl ester (CFSE) assay. The results showed that GD patients have significantly less Treg cells and more IL-17+ T cells. FOXP3 and miR-23a-3p were significantly down-regulated meanwhile SIRT1 and RORγt were up-regulated in GD patients. FOXP3 acetylation level of the GD group was lower than that of control groups. After EX-527 treatment, the percentage of Treg cells, expression and acetylation level of FOXP3 were significantly increased in the GD group. GD Tregs exhibited weaker suppressive activity, miR-23a-3p mimic suppressed SIRT1 expression and suppressive-activity of Tregs whereas it promoted the expression and acetylation level of FOXP3 in the GD group. Our findings suggest that the Treg function defect in GD patients is mediated by the abnormal acetylation of FOXP3, which is regulated by miR-23a-3p via targeting SIRT1.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Doença de Graves/metabolismo , MicroRNAs/metabolismo , Acetilação , Animais , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética
11.
J Cancer Res Ther ; 15(7): 1522-1529, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31939432

RESUMO

Objective: This study aimed to evaluate the safety and efficacy of thermal ablation in treating low-risk unifocal papillary thyroid microcarcinoma (PTMC). Materials and Methods: Patients with unifocal PTMC were enrolled in this study, and thermal ablations were performed. Contrast-enhanced ultrasound was used to estimate the extent of ablation immediately after thermal ablation; complications were recorded. The size and volume of the ablated area and thyroid hormones were measured, and the clinical evaluations were performed at 1, 3, 6, 12, and 18 months after thermal ablation. From July 2016 to July 2017, the prospective study was conducted involving 107 patients. Thermal ablation was well tolerated without serious complications. Results: Compared with the volume immediately after thermal ablation, the mean volume reduction ratio (VRR) of ablated lesions was 0.457 ± 0.218 (range: 0.040-0.979), 0.837 ± 0.150 (range: 0.259-1), 0.943 ± 0.090 (range: 0.491-1), 0.994-0.012 (range: 0.938-1), and 0.999 ± 0.002 (range: 0.992-1) at 1, 3, 6, 12, and 18 months after thermal ablation, respectively. Significant differences in the VRR were found between every two follow-up visits (P < 0.01). Results of patients' thyroid function test before thermal ablation and at 1 month after thermal ablation were normal, and no significant differences were observed (P > 0.05). No tumor regrowth, local recurrence, or distant metastases were detected during follow-up visits. Conclusion: Thermal ablation is a short-term safe and effective method in treating low-risk small PTMCs, which can be considered a potential alternative therapy for patients with PTMC.

12.
Cell Cycle ; 17(24): 2766-2778, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30523755

RESUMO

Tumor-associated macrophages (TAMs) were reported to be involved in colorectal cancer (CRC) progression. However, its biological role and underlying mechanism in CRC remained to be elucidated. In this study, the expressions of the macrophage marker CD68 and transforming growth factor ß1 (TGF-ß1) in CRC tumor tissues and adjacent tissues were detected by immunohistochemistry. The expression levels of miR-34a, TGF-ß1 and vascular endothelial growth factor (VEGF) in CRC tumor tissues and peripheral blood macrophages were measured by quantitative real-time PCR (qRT-PCR) and western blot. TGF-ß1 levels in culture supernatant were detected by ELISA. The cell proliferation and invasion of human CRC cell lines CL187 and HCT116 were determined by MTT assay and Transwell assay, respectively. The results showed that the expression of miR-34a was downregulated whereas TGF-ß1 and VEGF were upregulated in CRC tumor tissues and peripheral blood macrophages. TGF-ß1 secreted by TAMs promoted the proliferation and invasion of CRC cells. TGF-ß1-mediated miR-34a downregulation contributed to the proliferation and invasion of CRC cells via upregulating VEGF. MiR-34a in vivo exerted anti-tumor effect in CRC via inhibiting VEGF expression. In conclusion, TGF-ß1 secreted by TAMs promoted CRC proliferation and invasion through regulating miR-34a/VEGF axis.


Assuntos
Proliferação de Células , Neoplasias Colorretais/patologia , MicroRNAs/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Antagomirs/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética
13.
Arch Biochem Biophys ; 653: 63-70, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29702064

RESUMO

Recently, circular RNAs (circRNAs) have been demonstrated as essential regulators in human cancers. However, the function and mechanism of circRNAs in breast cancer (BC) remain largely unknown and require to be investigated. In the present study, we found that circMYO9B was highly expressed in BC tissues by bioinformatics analysis. And we showed that circMYO9B expression was positively correlated with patients' prognosis. Moreover, we found that circMYO9B knockdown significantly suppressed the proliferation, migration and invasion of BC cells in vitro. In vivo assays also indicated that circMYO9B silence delayed tumor growth. In mechanism, we found that circMYO9B promoted the expression of FOXP4 by sponging miR-4316 in BC cells. We showed that the expression of miR-4316 was inversely associated with that of circMYO9B or FOXP4 in BC tissues. Finally, we found that restoration of FOXP4 expression significantly reversed the effects of circMYO9B knockdown on BC cell proliferation, migration and invasion. In conclusion, our findings demonstrated a key role of circMYO9B/miR-4316/FOXP4 axis in regulating BC progression.


Assuntos
Neoplasias da Mama/patologia , Proliferação de Células/genética , Fatores de Transcrição Forkhead/genética , MicroRNAs/genética , Miosinas/sangue , Miosinas/genética , Invasividade Neoplásica/genética , RNA/fisiologia , Regulação para Cima/genética , Animais , Sequência de Bases , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade
14.
Oncol Res ; 23(4): 165-70, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27053345

RESUMO

Accumulating evidence has reported the significant role of miRNAs in the underlying biology of tumors, including breast cancer. The purpose for this study was to investigate the potential effects of miR-544a in breast cancer migration and invasion. The human normal breast Hs578Bst cells and the human breast cancer MCF-7 and MDA-MB-231 cells were used to analyze the expression of miR-544a by RT-PCR. The effects of miR-544a on the two kinds of breast cancer cell migration and invasion were analyzed using the Matrigel and Transwell assay, respectively. miR-544a expression on the cell metastasis-related protein expression was also analyzed using Western blotting. Compared to the normal Hs578Bst cells, miR-544a was significantly downregulated in MCF-7 cells but was upregulated in MDA-MB-231 cells (p < 0.01). The overexpressed miR-544a significantly promotes the migrated and invaded MCF-7 cells (p < 0.05), which was opposite to that in MCA-MB-231 cells (p < 0.05). Moreover, the cadherin 1 (CDH1) expression was negatively correlated to miR-544a expression in the two kinds of cells. Our study suggested that the overexpressed miR-544a may be a promoter for breast cancer migration and invasion by targeting CDH1.


Assuntos
Neoplasias da Mama/metabolismo , Caderinas/genética , MicroRNAs/fisiologia , Antígenos CD , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Caderinas/metabolismo , Movimento Celular , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Invasividade Neoplásica , Interferência de RNA
15.
Tumour Biol ; 37(7): 9037-43, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26762408

RESUMO

Recent studies have shown that the lymphocyte to monocyte ratio (LMR) is a useful prognostic factor in various cancers. The purpose of the current study was to investigate the association between pretreatment LMR, disease-free survival (DFS), and overall survival (OS) in patients with early-stage (I to III) triple-negative breast cancer (TNBC). Pretreatment LMR with corresponding clinical features from 230 TNBC patients was noted. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff values for LMR, lymphocyte, and monocyte counts. The difference between variables was calculated using chi-square tests. The Kaplan-Meier method and univariate and multivariate Cox regression models were applied to assess OS and DFS. Based on the ROC analysis, the optimal cutoff point for LMR was 4.7. Associations between high LMR (≥4.7) and significantly small tumor size (P = 0.005) and TNM stage (P = 0.013) were found, although there was no significant association for other clinical pathological factors. In the multivariate analysis, LMR was a significant predictive factor for both OS (hazard ratio [HR] = 0.42; 95 % confidence interval [CI], 0.19-0.95; P < 0.001) and DFS (HR = 0.40; 95 % CI, 0.20-0.79; P < 0.001). In addition, the predictive values of the OS and DFS were also observed for absolute counts of lymphocytes (P < 0.001) and monocytes (P < 0.001). Our study suggests that pretreatment LMR may be a predictive factor for long-term survival in patients with early-stage TNBC.


Assuntos
Linfócitos/patologia , Monócitos/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Estudos Retrospectivos
16.
Iran J Basic Med Sci ; 19(12): 1331-1336, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28096966

RESUMO

OBJECTIVES: Vascular calcification is one the major characteristics in patients with various types of chronic inflammatory disorders. MiRNAs have been shown to be involved in many normal biological functions as well as diseases; however, their role in vascular calcification has not received much attention. MATERIALS AND METHODS: In the current study, we built a vascular calcification rat model using vitamin D3 plus nicotine and analyzed miRNA expression profile by miRNA chip assay. Potential target of one selected miRNA with sharpest variation in expression were predicted by both PicTar and TargetScan. The impact of the selected miRNA on the expression of the potential target on both mRNA and protein levels were measured by RT-PCR and Western blot, respectively. RESULTS: Our results identified 16 dysregulated miRNAs, among which miR-297a showed the sharpest variation. Further analysis focusing on miR-297a revealed that fibroblast growth factor 23 (FGF23) was a potential target of miR297a. Measurement of FGF23 and its regulator Klotho on both mRNA and protein levels demonstrated that FGF23 was significantly increased while Klotho was decreased in rats with vascular calcification. CONCLUSION: Our results indicated that FGF23 was target of miR-297a and decreased miR-297a in vascular calcification lead to the increase of FGF23, which together with Klotho might enhance vascular calcification. The findings of this study could provide valuable information for the understanding of mechanisms underlying miR-dependent vascular calcification as well as potential treatment target for the disease.

17.
Clin Res Hepatol Gastroenterol ; 40(2): 246-53, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26387842

RESUMO

BACKGROUND AND OBJECTIVE: The prognostic value of Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) in gastric cancer remains controversial. To further investigate this relationship, we performed meta-analyses to systematically review the association between LGR5 expression and various clinical parameters in gastric cancer patients. METHOD: Eligible studies from PubMed, Embase, Web of Science, CNKI (Chinese National Knowledge Infrastructure), Wangfang (Database of Chinese Ministry of Science & Technology) and CBM (China Biological Medicine) databases were evaluated to investigate the association of LGR5 expression with overall survival (OS) and clinicopathological features of gastric cancer. RESULTS: LGR5 overexpression was significantly associated with poor OS in patients with gastric cancer (HR 1.66, 95% CI 1.02-2.69). LGR5 overexpression was also significantly associated with TNM stage (TIII/TIV vs TI/TII: OR 5.42, 95% CI 1.02-28.72) and lymph node metastasis (positive vs negative: OR 2.30, 95% CI 1.06-5.0). CONCLUSIONS: Our meta-analysis indicates that LGR5 may be a predictive factor for invasion and metastasis, and poor prognosis in patients with gastric cancer.


Assuntos
Receptores Acoplados a Proteínas-G/biossíntese , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Neoplasias Gástricas/patologia , Taxa de Sobrevida
18.
Med Oncol ; 32(10): 238, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26330362

RESUMO

Hepatotoxicity induced by sorafenib and antiviral therapy is a limitation for its continuation treatment for patients with advanced hepatitis B virus-related hepatocellular carcinoma (HCC). This prospective study determined the efficacy of tiopronin in hepatotoxicity prevention of HBV-related HCC treatment. Eighty-two patients (median age, 50 years; 71 % male) of advanced HCC treated with sorafenib and antiviral therapy were included, of whom 40 were given the supplementation of tiopronin. The primary endpoint was liver function which was checked before the treatment and every week during the therapy. Besides, course discontinuations, dose reductions, HBV DNA levels and treatment efficacy were evaluated. Patient characteristics and liver function were comparable (p > 0.05). The proportion of abnormal liver function was significantly lower in tiopronin group than in control group including alanine transaminase (ALT, p = 0.035), aspartate aminotransferase (AST, p = 0.041), total bilirubin (TBIL, p = 0.021) and albumin (ALB, p = 0.001). Rates of course discontinuations (p = 0.024) and dose reductions (p = 0.046) were significantly lower in tiopronin groups, and disease control rate (p = 0.036) was higher. No difference was found in HBV DNA level. Multivariate regression analysis showed that sorafenib (OR 7.837; 95 % CI 3.845-15.333; p = 0.004), antiviral therapy (OR 3.871; 95 % CI 1.572-9.569; p = 0.044) and hepatoprotective drug (OR 3.007; 95 % CI 1.321-6.308; p = 0.046) played important roles in clinical outcome. Tiopronin tends to prevent the HCC patients from the treatment-induced hepatotoxicity, enhance patients' tolerance to sorafenib and antiviral therapy and even improve the cancer treatment efficacy.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Tiopronina/uso terapêutico , Antineoplásicos/efeitos adversos , Antivirais/efeitos adversos , Carcinoma Hepatocelular/virologia , Quimioterapia Combinada , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Fígado/lesões , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Sorafenibe
19.
Biomed Res Int ; 2015: 954870, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26090465

RESUMO

The Polo-like kinase 1 (PLK1) is one member of the so-called Polo-like kinase family which plays an important role in tumorigenesis. By analyzing the potential complementary microRNA (miRNA) targeting sequence of PLK1, we identified that miRNA-3686 (hereby and thereafter mir3696) could be the potential regulator for PLK1. Real-time PCR demonstrated that the mir3686 has a relatively higher expression in the immortalized pancreas cell HPDE6C7 than pancreas carcinoma derived cell line PANC1. The upregulation of mir3686 in HPDE6C7 cell corresponded with the low expression of PLK1 as well. Both luciferase based reporter assay and evaluation of endogenous PLK1 expression demonstrated that mir3686 regulated PLK1, which confirms our speculation. Moreover, we found that transfection of mir3686 in PANC1 cell could lead to proliferation inhibition and promote apoptosis. Further analysis demonstrated that mir3686 transfection in PANC1 cell also inhibited cell invasion, and clone formation in cell invasion assay and clonogenic cell survival assay, respectively. In contrast, inhibition of mir3686 expression in HPDE6C7 cell enhanced the capability of proliferation, cell invasion and clone formation. Taken together, our results indicated that mir3686 could target PLK1 to inhibit the cell proliferation in pancreas cancer derived cell line and mir3686 could be a new therapeutic target for pancreas cancer treatment.


Assuntos
Carcinoma/genética , Proteínas de Ciclo Celular/genética , MicroRNAs/biossíntese , Neoplasias Pancreáticas/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Apoptose/genética , Carcinoma/patologia , Proteínas de Ciclo Celular/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Proto-Oncogênicas/biossíntese
20.
Int J Mol Med ; 35(5): 1395-402, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25738546

RESUMO

Breast cancer (BC) is the foremost cause of cancer-related mortality in women worldwide. An increasing number of studies has confirmed that microRNAs (miRNAs or miRs) play an important role in the development and progression of BC. microRNA-214 (miR-214), a member of the miRNA family, has been demonstrated to function as both a tumor suppressor and oncogene in various types of human cancer. However, the biological function of miR-214 in BC remains unclear. The present study was designed to investigate the potential role of miR-214 in the development and progression of BC. Our results revealed that miR-214 expression was significantly increased in the BC tissues compared with the adjacent benign tissues, and that the upregulation of miR-214 was significantly associated with the invasion ability of the BC cells. Furthermore, p53, which has been reported to be downregulated in BC, was predicted to be the target gene of miR-214 using bioinformatics software programs. Moreover, luciferase reporter vectors were constructed and it was confirmed that p53 is a target of miR-214. Following the transfection of miR-214 into BC cells, we found that the overexpression of miR-214 markedly enhanced cell invasion through the downregulation of p53 expression. By contrast, the overexpression of p53 abrogated the effects of miR-214. In conclusion, this study demonstrates that miR-214 functions as an oncogene in BC, at least partly by promoting cell invasion through the downregulation of p53. Therefore, miR-214 may be a potential therapeutic target for the treatment of BC.


Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Interferência de RNA , RNA Mensageiro/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Biologia Computacional , Bases de Dados de Ácidos Nucleicos , Regulação para Baixo , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/química , Pessoa de Meia-Idade , Invasividade Neoplásica , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Proteína Supressora de Tumor p53/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA