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1.
Cell Mol Biol (Noisy-le-grand) ; 65(6): 64-72, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472049

RESUMO

Breast cancer is a malignant tumor that occurs in the glandular epithelial tissues of the breast. It is one of the most common malignant tumors in women. This study was aimed at investigating the role of cell-free DNA (cfDNA) as a potential biomarker for breast cancer diagnosis. Patients with primary breast cancer (n =110) were enrolled in the experimental group, 95 patients with benign breast tumors were in control group 1, while 90 healthy volunteers were in control group 2. Quantitative PCR was used to determine cfDNA concentration and integrity in each group. The cfDNA levels in different groups and their relationship with clinical features of breast cancer patients were analyzed. Receiver operational curves were established to analyze sensitivity and specificity of cfDNA concentration, cfDNA integrity, CEA, CA125 and CA15-3. The cfDNA concentration and cfDNA integrity of the experimental group were significantly higher than those of control groups 1 and 2. The cfDNA concentration and integrity in plasma of experimental group after chemotherapy were significantly lower than those before chemotherapy. While CEA and CA15-3 expressions were significantly correlated with cfDNA concentration, CA125 expression was significantly correlated with cfDNA integrity. Results from ROC curve analysis showed that the sensitivity and specificity of cfDNA concentration and integrity were higher than those of traditional tumor biomarkers. These results indicate that cfDNA concentration and integrity are significantly higher in primary breast cancer patients than in benign breast tumor patients and healthy people. Thus, cfDNA may serve as a potential biomarker of breast cancer.


Assuntos
Neoplasias da Mama/sangue , Ácidos Nucleicos Livres/sangue , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ácidos Nucleicos Livres/genética , DNA de Neoplasias/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Adulto Jovem
2.
Tumour Biol ; 37(6): 7431-40, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26678886

RESUMO

Accumulating evidence strongly suggests that dysregulation of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. However, the biological role of HOTTIP in colorectal cancer (CRC) has not yet been discussed. Here, we report that HOTTIP acts as a functional oncogene in the pathogenesis of CRC. In this study, quantitative polymerase chain reaction (qPCR) was performed to detect the expression of HOTTIP in 48 pairs of colorectal cancer samples. We found that overexpression of HOTTIP is correlated with an advanced pathological stage and a larger tumor size. Moreover, functional analyses revealed that the knockdown of HOTTIP expression by small interfering RNA (siRNA) or small hairpin RNA (shRNA) could inhibit cell proliferation and induce cell apoptosis. More importantly, we observed that HOTTIP knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in both DLD-1 cells and SW480 cells. An in vivo experiment also revealed that the knockdown of HOTTIP inhibited tumor growth. Western blot and immunohistochemistry analyses indicated that HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. Collectively, our results suggest that HOTTIP is involved in the progression of CRC and may provide evidence for HOTTIP being a target for therapy of this disease.


Assuntos
Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias Colorretais/patologia , Inibidor de Quinase Dependente de Ciclina p21/antagonistas & inibidores , Inativação Gênica , RNA Longo não Codificante/genética , RNA Interferente Pequeno/genética , Animais , Apoptose , Western Blotting , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Progressão da Doença , Feminino , Citometria de Fluxo , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Mol Cancer ; 14: 51, 2015 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-25742952

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes, such as cell growth and apoptosis. The SPRY4 intronic transcript 1 (SPRY4-IT1) is a 708-bp lncRNA on chromosome 5 with a potential functional role in tumorigenesis. The clinical significance of SPRY4-IT1 and the effect of SPRY4-IT1 on cancer progression are unclear. METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of SPRY4-IT1 in 48 breast cancer tissues and four breast cancer cell lines. Gain and loss of function approaches were used to investigate the biological role of SPRY4-IT1 in vitro. Microarray bioinformatics analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by rescue experiments, and by western blotting and qRT-PCR. RESULTS: SPRY4-IT1 expression was significantly upregulated in 48 breast cancer tumor tissues comparedwith normal tissues. Additionally, increased SPRY4-IT1 expression was found to be associated with a larger tumor size and an advanced pathological stage in breast cancer patients. The knockdown of SPRY4-IT1 significantly suppressed proliferation and caused apoptosis of breast cancer cells in vitro. Furthermore, we discovered that ZNF703 was a target of SPRY4-IT1 and was downregulated by SPRY4-IT1 knockdown. Moreover, we provide the first demonstration that ZNF703 plays an oncogenic role in ER (-) breast carcinoma cells. CONCLUSIONS: SPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer.


Assuntos
Neoplasias da Mama/genética , Proteínas de Transporte/genética , Proliferação de Células/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , RNA Longo não Codificante/genética , Regulação para Cima/genética , Apoptose/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Pessoa de Meia-Idade
4.
Public Health Nutr ; 18(18): 3355-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25776573

RESUMO

OBJECTIVE: There have been inconsistent results published regarding the relationship between dyslipidaemia and an increased risk of colorectal neoplasia (CRN), including colorectal adenoma (CRA) and colorectal cancer (CRC). We conducted a meta-analysis to explore the relationship between dyslipidaemia and CRN. DESIGN: We identified studies by performing a literature search using PubMed, EMBASE and the Science Citation Index through October 2013. SETTING: We analysed thirty-three independent studies reporting the association between CRN and at least one of the selected lipid components, including total cholesterol (TC), TAG, HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C). SUBJECTS: CRN cases (n 21 809) were identified. RESULTS: Overall, people with high levels of serum TAG (risk ratio (RR)=1.08; 95% CI 1.05, 1.12, P<0.00001) and LDL-C (RR=1.07; 95% CI 1.00, 1.14, P=0.04) presented an increased prevalence of CRN. Subgroup analyses revealed that high levels of serum TC (RR=1.04; 95% CI 1.01, 1.09, P=0.02), TAG (RR=1.06; 95% CI 1.03, 1.10, P=0.0009) and LDL-C (RR=1.11; 95% CI 1.04, 1.19, P=0.003) increased the risk of CRA but not of CRC. No association between serum HDL-C and risk for CRN (including CRA and CRC) was observed. CONCLUSIONS: Both TAG and LDL-C were significantly associated with an increasing prevalence of CRN. High levels of serum TC, TAG and LDL-C were positively associated with CRA but not with CRC. No significant association was observed between levels of serum HDL-C and CRN.


Assuntos
Adenoma/etiologia , Neoplasias Colorretais/etiologia , Dislipidemias/fisiopatologia , Adenoma/sangue , Adenoma/epidemiologia , Adulto , Colesterol/sangue , LDL-Colesterol/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Humanos , Hipercolesterolemia/fisiopatologia , Hipertrigliceridemia/fisiopatologia , Incidência , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Triglicerídeos/sangue
5.
Thorac Cancer ; 14(14): 1316-1319, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36965139

RESUMO

One year following bladder cancer surgery, a 65-year-old man had computed tomography (CT) that revealed bilateral pulmonary nodules. Pulmonary wedge resections were performed after the nodules were found to grow in follow-up. Unusually, we found that these two lesions were not homologous, nor were they metastases from prior bladder cancer, and therefore, synchronous double primary lung cancer (sDPLC) was diagnosed. The immunohistochemical findings excluded the possibility of bladder cancer metastasis, but could not determine whether they were from the same source. Next generation sequencing (NGS) supported the diagnosis sDPLC because they amply demonstrated the two sources' distinct origins. Finally, after discussion with pathologists, this patient was diagnosed as small cell lung carcinoma (SCLC) and received postoperative EP chemotherapy. We also documented a few rather uncommon alterations that might serve as a foundation for further investigation. This case suggests that in addition to immunohistochemical, NGS is also helpful to clarify the etiology and refine the pathological classification of tumors, which has guiding significance for the establishment of precise diagnosis and optimal treatment.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Neoplasias da Bexiga Urinária , Masculino , Humanos , Idoso , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos
6.
Open Med (Wars) ; 17(1): 135-150, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35071775

RESUMO

Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis and is the second most fatal cancer, and certain HCC patients also show high heterogeneity. This study developed a prognostic model for predicting clinical outcomes of HCC. RNA and microRNA (miRNA) sequencing data of HCC were obtained from the cancer genome atlas. RNA dysregulation between HCC tumors and adjacent normal liver tissues was examined by DESeq algorithms. Survival analysis was conducted to determine the basic prognostic indicators. We identified competing endogenous RNA (ceRNA) containing 15,364 pairs of mRNA-long noncoding RNA (lncRNA). An imbalanced ceRNA network comprising 8 miRNAs, 434 mRNAs, and 81 lncRNAs was developed using hypergeometric test. Functional analysis showed that these RNAs were closely associated with biosynthesis. Notably, 53 mRNAs showed a significant prognostic correlation. The least absolute shrinkage and selection operator's feature selection detected four characteristic genes (SAPCD2, DKC1, CHRNA5, and UROD), based on which a four-gene independent prognostic signature for HCC was constructed using Cox regression analysis. The four-gene signature could stratify samples in the training, test, and external validation sets (p <0.01). Five-year survival area under ROC curve (AUC) in the training and validation sets was greater than 0.74. The current prognostic gene model exhibited a high stability and accuracy in predicting the overall survival (OS) of HCC patients.

7.
Ann Transl Med ; 10(16): 895, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36110989

RESUMO

Background: To research the correlation between the prognosis of patients suffering from lung adenocarcinoma (LUAD) and methyltransferase like 7B (METTL7B) expression. Methods: The Cancer Genome Atlas (TCGA) database was utilized to verify METTL7B expression, and The Human Protein Atlas database was utilized to verify METTL7B expression at the tissue level. The relationship between METTL7B and LUAD prognostic data was then analyzed using the KM-plotter database. The correlation between METTL7B expression and immune cells was demonstrated through the TIMER database. For exploring the possible mechanism of action, gene set enrichment analysis (GSEA) was performed. Finally, the role of METTL7B in the adverse biological events of LUAD was further explored by in vitro experiments such as proliferation and invasion assays. Results: As per the TCGA database, METTL7B expression was increased in cancerous tissues compared with paracancerous tissues, and it was mostly located in the cytoplasm. Patients suffering from LUAD who had low METTL7B expression had a relatively better overall survival (OS) and disease-specific survival (DSS) according to the Kaplan-Meier-plotter (KM-plotter) database. METTL7B expression was significantly associated with immune cell infiltration in LUAD patients, as shown by correlation analysis. GSEA revealed that METTL7B may affect the physiological events of LUAD by playing a part in cell cycle regulation. In vitro cytological experiments demonstrated that METTL7B can markedly affect the metastasis of LUAD cells. Conclusions: The reduction of METTL7B expression can prolong OS and DSS in LUAD patients. It may be utilized as a novel predictive biomarker of LUAD, and may be associated with immune infiltration of LUAD. Interfering with METTL7B expression can significantly cause inhibition of LUAD by modulating the ability of cells to proliferate and migrate. These results point to a possible target for developing anti-cancer therapies against LUAD.

8.
Artif Cells Nanomed Biotechnol ; 48(1): 393-407, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31913710

RESUMO

LncRNA PTENP1 is a competitive endogenous RNA (ceRNA) involved in decoying miR-106b in multiple diseases. This study investigates the interaction of PTENP1 and miR-106b in cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) in cervical cancer. The expressions of PTENP1, miR-106b and PTEN were determined in cervical cancer tissues, adjacent normal tissues, cervical cancer cells (HeLa, SiHa, C33A and CasKi) and normal cervical epithelial H8 cells. Up-regulation of PTENP1 and down-regulation of miR-106b were conducted in HeLa and CasKi cells by transfecting cells with corresponding miRNA mimics and inhibitors. Bioinformatics analysis, luciferase reporter assay and RNA-pull down assay were performed to verify the association of miR-106b, PTEN, and PTENP1. Cell growth and cell apoptosis were determined by CCK-8 and flow cytometry analysis. It was found that the expressions of PTENP1 and PTEN were up-regulated and that of miR-106b were down-regulated in cervical cancer tissues and cells. PTENP1 localized in cytoplasm and competitively bound to miR-106b. Up-regulation of PTENP1 and down-regulation of miR-106b contributed to increased expressions of PTEN and E-cadherin. Decreased expression of miR-106b, ZEB1, Snail and Vimentin, resulted in inhibiting cell proliferation and promoting cell apoptosis. Over-expression of PTENP1 and miR-106b accelerated cell proliferation and slowed down cell apoptosis. miR-106b inhibited the expression of PTEN. Our results suggest that LncRNA PTENP1 inhibits cervical cancer progression by competitively binding to miR-106b, leading to promote PTEN expression, inhibit cell proliferation and EMT and induce cell apoptosis in cervical cancer cells.


Assuntos
Apoptose , Regulação Leucêmica da Expressão Gênica , Genes Supressores de Tumor , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Neoplasias do Colo do Útero/metabolismo , Feminino , Células HeLa , Humanos , MicroRNAs , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
9.
Front Oncol ; 10: 571521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33680914

RESUMO

The clinical significance of mutation in multiple pulmonary nodules is largely limited by single gene mutation-directed analysis and lack of validation of gene expression profiles. New analytic strategy is urgently needed for comprehensive understanding of genomic data in multiple pulmonary nodules. In this study, we performed whole exome sequencing in 16 multiple lung nodules and 5 adjacent normal tissues from 4 patients with multiple pulmonary nodules and decoded the mutation information from a perspective of cellular functions and signaling pathways. Mutated genes as well as mutation patterns shared in more than two lesions were identified and characterized. We found that the number of mutations or mutated genes and the extent of protein structural changes caused by different mutations is positively correlated with the degree of malignancy. Moreover, the mutated genes in the nodules are associated with the molecular functions or signaling pathways related to cell proliferation and survival. We showed a developing pattern of quantity (the number of mutations/mutated genes) and quality (the extent of protein structural changes) in multiple pulmonary nodules. The mutation and mutated genes in multiple pulmonary nodules are associated with cell proliferation and survival related signaling pathways. This study provides a new perspective for comprehension of genomic mutational data and might shed new light on deciphering molecular evolution of early stage lung adenocarcinoma.

10.
Nutrients ; 8(5)2016 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-27144580

RESUMO

Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.


Assuntos
Colite/complicações , Neoplasias Colorretais/prevenção & controle , Glutamina/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Neoplasias Colorretais/etiologia , Dieta , Regulação da Expressão Gênica/efeitos dos fármacos , Glutamina/administração & dosagem , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Serina-Treonina Quinases TOR/genética
11.
Artigo em Zh | MEDLINE | ID: mdl-15840940

RESUMO

The effects and the relationship between soaking rice seed of exogenous glucose, fructose and nitric oxide (NO) donor sodium nitroprusside (SNP) on the seed germination under salt stress were investigated. The results showed that employment of exogenous fructose, glucose and NO donor SNP could significantly promote the germination index and the early germination rate of rice seed under salt stress. Also, SNP pretreatment enhanced endogenous glucose and fructose contents. Effects of exogenous glucose and fructose combined with different concentrations of SNP on the rice seed germination and seedling growth under salt stress were surveyed. The results also showed that there existing positive effect of application of glucose plus SNP on the rice seed germination in comparison with existing a few negative effects of fructose plus SNP pretreatment. Additionally, the alleviation of inhibition of early rice seedling growth under salt stress by SNP could be modulated by glucose and fructose pretreatment, also the effect of glucose was stronger.


Assuntos
Frutose/farmacologia , Germinação/efeitos dos fármacos , Glucose/farmacologia , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Cloreto de Sódio/farmacologia , Fatores de Tempo
12.
J Exp Clin Cancer Res ; 34: 100, 2015 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-26362196

RESUMO

BACKGROUND: Aberrant expression of long noncoding RNAs (lncRNAs) has frequently been reported in cancer studies, including those of colorectal cancer (CRC). Increasing evidence suggests that lncRNAs are significantly correlated with the pathogenesis, development and metastasis of cancer. Loc554202 is a 2166-bp transcript on human chromosome 9p21.3, the expression of which is dysregulated in breast and lung cancer cells. However, its role in CRC remains under investigation. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to assess the relative expression of Loc554202 in CRC cell lines and tissues. Gain and/or loss of function approaches were used to investigate the potential functional roles in cell proliferation and apoptosis in vitro and in vivo. qRT-PCR, western-blotting and immunohistochemistry were used to evaluate the mRNA and protein expression of apoptosis-related factors. RESULTS: Loc554202 was significantly downregulated in cancerous tissues and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Low Loc554202 expression was closely associated with advanced pathologic stage and a larger tumor size. The overexpression of Loc554202 decreased the cell proliferation and induced apoptosis in vitro and hindered tumorigenesis in vivo. Loc554202 regulated cell apoptosis partly through the activation of specific caspase cleavage cascades. CONCLUSION: Our results suggest that Loc554202 may play an important role in the progression of CRC and could be a candidate prognostic biomarker or a target for new cancer therapies.


Assuntos
Apoptose , Caspases/metabolismo , Neoplasias Colorretais/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Proliferação de Células , Neoplasias Colorretais/enzimologia , Ativação Enzimática , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Expressão Gênica , Células HCT116 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias
13.
PLoS One ; 9(7): e102477, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25029444

RESUMO

To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible studies were identified through a systematic literature review from PubMed, EMBASE, and the Science Citation Index up to February 2014. A combined analysis was performed, followed by a subgroup analyses stratified by the study design. We used data collected from 8 prospective studies involving respectively a total of 9243 participants and 4310 CRN cases which including 438 patients with colorectal adenoma (CRA), and 3873 patients with colorectal carcinoma (CRC). The pooled data from this meta-analysis indicated there was no significant association between APOE polymorphism and CRN (ε2: P = 0.51, OR 1.04 95% CI 0.93 to 1.16; ε4: P = 0.72, OR 0.98 95% CI 0.90 to 1.07). Interestingly, subgroup analysis demonstrated there was a significant decreased risk for proximal CRN in patients with APOE ε4 (P = 0.0007, OR 0.52 95% CI 0.35 to 0.76). Data showed no significant association between APOE genotype and overall CRN. However, compared with those carry APOE ε3 alleles, persons with APOE ε4 genotype have significant decreased risk suffering from proximal CRN but not from distal CRN.


Assuntos
Apolipoproteínas E/genética , Neoplasias Colorretais/genética , Polimorfismo Genético , Frequência do Gene , Genótipo , Humanos , Razão de Chances
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