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Biosci Rep ; 41(2)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33501930


BACKGROUND: Both meta-analyses and systematic reviews were used to assess the relationship between purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) rs3751143 polymorphism and the risk of cancer. MATERIALS AND METHODS: The data used in this research were collected from Google Scholar, Web of Science, CNKI, and Wan Fang Data databases. The final retrieval ended on 22 February 2019. The strength of correlation was assessed using odds ratios and 95% confidence intervals. Based on the heterogeneity test results, fixed-effect (Mantel-Haenszel) or random-effects (DerSimonian-Laird) models were selected to summarise the collective effects. RESULTS: Eight separate studies containing 1462 cancer cases and 3037 controls were enrolled. Overall, there was no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, or recessive models. CONCLUSIONS: Our meta-analysis indicates that there is no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, and recessive models.

Cancer Manag Res ; 12: 3069-3078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431549


Background: NUDT21, an RNA binding protein, has been reported to play an important role in the regulation of multiple biological responses. Detection of NUDT21 expression may lead to the identification of a novel marker for breast cancer. Purpose: The aim of this study was to investigate the clinical significance and functional role of NUDT21 in breast cancer. Methods: The protein expression of NUDT21 was examined by immunohistochemistry (IHC) in 100 paraffin-embedded, archived breast cancer samples and 100 benign breast tissues. Then, the correlations between the NUDT21 expression and clinicopathologic characteristics and prognoses of the breast cancer patients were analyzed. In addition, the function of NUDT21 in breast cancer cell lines was detected by the methyl thiazolyl tetrazolium, colony formation and transwell assays. Finally, mass spectrometry analysis and Western blotting were used to identify the proteins that interact directly with NUDT21. Results: IHC analysis revealed that the expression of NUDT21 was significantly lower in breast cancer tissues compared with benign breast disease tissues. The correlation analysis revealed that low expression of NUDT21 was positively correlated with tumor size, lymph node metastasis, and TNM stage. Also, Kaplan-Meier survival curves showed that patients with lower NUDT21 expression had shorter overall survival and relapse-free survival compared with higher NUDT21 expression. In addition, the knockdown of NUDT21 enhanced cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Consistently, the overexpression of NUDT21 inhibited cell proliferation, migration, invasion, and EMT. In addition, NUDT21 directly interacted with CPSF6 and negatively regulated its expression. Moreover, the knockdown of CPSF6 reversed NUDT21 expression-induced cancer cell migration and invasion. Conclusion: NUDT21 might play a tumor-suppressive role by inhibiting cell proliferation and invasion via the NUDT21/CPSF6 signaling pathway in breast cancer cells.

Gynecol Endocrinol ; 36(2): 148-151, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31248316


This study determined the effect of exogenous soluble receptor for advanced glycation end products (sRAGE) on the pro-inflammatory activities that occur during polycystic ovary syndrome (PCOS) in human follicular cells and explored a potential mechanism for preventing the development of inflammation. Follicular fluid was allocated into one of three treatment groups (0, 0.6, and 1.2 µg mL-1 of sRAGE). Collectively, these results indicate that exogenous sRAGE supplementation alleviates inflammation in ovarian follicular granulosa cells by regulating p-ERK and AP-1 signaling.

Células da Granulosa/metabolismo , Inflamação/metabolismo , Síndrome do Ovário Policístico/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Adulto , Citocinas/metabolismo , Feminino , Líquido Folicular/metabolismo , Humanos , Fosforilação , Fator de Transcrição AP-1/metabolismo
Arch Biochem Biophys ; 657: 23-30, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30222949


microRNA (miR)-141-3p has context-dependent effects on tumor progression. In this study, we attempted to explore the expression and function of miR-141-3p in cervical cancer. We found that miR-141-3p expression was significantly increased in cervical cancer specimens relative to normal cervical tissues. Moreover, miR-141-3p levels were associated with tumor size and lymph node metastasis status. Ectopic expression of miR-141-3p significantly increased cervical cancer cell proliferation, colony formation, invasion, and epithelial to mesenchymal transition, whereas depletion of miR-141-3p suppressed cervical cancer cell proliferation and invasion. FOXA2 was identified to be a target of miR-141-3p. Overexpression of miR-141-3p led to a marked inhibition of endogenous FOXA2 in cervical cancer cells. FOXA2 silencing phenocopied the effects of miR-141-3p overexpression on cervical cancer cell proliferation and invasion. Enforced expression of FOXA2 blocked the effects of miR-141-3p on cervical cancer cell proliferation and invasion. miR-141-3p overexpression significantly accelerated the growth of xenograft tumors, which was accompanied by a striking reduction in FOXA2 expression. miR-141-3p acts as an oncogene in cervical cancer largely through repression of FOXA2. Targeting miR-141-3p may represent a potential therapeutic strategy for cervical cancer.

Carcinogênese/genética , Fator 3-beta Nuclear de Hepatócito/genética , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Regulação para Cima , Neoplasias do Colo do Útero/patologia
Ann Surg Oncol ; 18(2): 580-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20803081


BACKGROUND: Inhibition of mammalian target of rapamycin (mTOR) represents an attractive target for anticancer therapy, but its role in suppression of colorectal cancer (CRC) cell growth by cyclooxygenase-2 (COX-2) inhibitors is unclear. Here, we analyzed the effect of indomethacin (Indo, a nonselective COX-2 inhibitor) and nimesulide (Nim, a selective COX-2 inhibitor) on mTOR signaling in CRC cells in vitro and in vivo to determine the dependence of this effect on COX-2. METHODS: Human CRC cell lines with varying COX-2 expression levels were treated with Indo and Nim. Western blot test was performed to detect mTOR-related components (mTOR, p70s6 K, and 4EBP1), and cell viability, cell cycle, and apoptosis were assessed. HCT116 and SW1116 cells were injected into athymic nude mice to establish a CRC xenograft model. After treatment with Nim, tumor volume, mTOR signaling, and apoptosis were evaluated in this model. HT29 and SW1116 cells were also treated with Nim after transfection with COX-2-specific small interfering RNA (siRNA) to assess dependence of COX-2 on mTOR signaling under drug treatment. RESULTS: Both Indo and Nim reduced mTOR signaling activity in CRC cells that differ in their COX-2 expression in vitro and in vivo. Additionally, Indo and Nim could reduce the mTOR signaling activity after COX-2 silencing in CRC cells. CONCLUSIONS: mTOR signaling is involved in Indo- and Nim-mediated suppression of CRC growth via a COX-2 independent pathway. This study unveils a novel mechanism through which COX-2 inhibitors exerts their anticancer effects and further emphasizes targeting mTOR signaling in anticancer therapy.

Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/química , Indometacina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/genética , Células Tumorais Cultivadas
Dig Dis Sci ; 55(11): 3138-46, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20127415


BACKGROUND AND AIMS: The function of human macrophage metalloelastase (HME) also known as matrix metalloproteinase 12, in tumorigenesis is contradictory. The current study was designed to investigate the association of HME expression with angiogenesis and prognosis of gastric carcinomas. METHODS: In situ hybridization and immunohistochemistry were used to detect HME in human gastric carcinomas, chronic gastritis with atypical hyperplasia, and normal gastric epithelium mucosa. The results were further confirmed by RT-PCR or semi-quantitative reverse transcription polymerase chain reaction and Western blotting in gastric carcinomas and paired noncancerous tissues. VEGF and microvessel density count were also detected by immunohistochemical staining in all carcinoma tissues. The prognostic significance of HME was assessed with multiple linear regression analysis and Cox proportional hazards model. RESULTS: High expression of HME protein/mRNA was observed in gastric carcinomas and atypical hyperplasia tissues compared with normal gastric epithelium mucosa, or paired noncancerous tissues. HME protein/mRNA were negatively correlated with MVD (p < 0.01), VEGF (p < 0.01), tumor differentiation grade (p < 0.05), vascular invasion (p < 0.01), and recurrence (p < 0.05-0.01). HME protein was an independent influential factor of MVD (p < 0.01). HME protein/mRNA was an independent prognostic factor of gastric carcinoma (p < 0.05-0.01). Patients with overexpression of HME protein/mRNA demonstrated a significantly better survival rate compared with those who did not (p < 0.05-0.01). CONCLUSIONS: Overexpression of HME is strongly correlated with the reduced angiogenesis and vascular invasion of gastric carcinoma, and may serve as a useful predictive indicator in patients with this disease.

Gastrite/metabolismo , Metaloproteinase 12 da Matriz/metabolismo , Neovascularização Patológica/enzimologia , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Western Blotting , Doença Crônica , Progressão da Doença , Feminino , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise de Sobrevida