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1.
Anticancer Res ; 39(9): 4637-4642, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519561

RESUMO

AIM: The aim of this study was to characterize the role of Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis chromosomal region gene 1 (AMMECR1) in human lung cancer cell lines. MATERIALS AND METHODS: AMMECR1 gene expression was evaluated in four lung cell lines, with A549 then selected for further in-depth examination. To characterize the role of AMMECR1, silencing was achieved utilizing lentivirus-mediated RNA interference, and confirmed by quantitative real-time polymerase chain reaction and western blotting. The impact of AMMECR1 silencing on cellular proliferation was assessed using Celigo-based and MTT assays. Apoptosis was determined using the annexin V-allophycocyanin single staining method. Cell-cycle arrest was assessed by flow cytometry. Finally, colony formation was assessed using Giemsa staining. RESULTS: In A549 cells, AMMECR1 silencing was found to significantly suppress cell proliferation, reduce colony formation, promote apoptosis, and arrest cells in the S and G2/M phases. CONCLUSION: AMMECR1 plays a critical role in cell proliferation, cell-cycle progression, and apoptosis of human lung cancer cells, and may serve as a potential therapeutic target for non-small-cell lung cancer.


Assuntos
Apoptose/genética , Ciclo Celular/genética , Neoplasias Pulmonares/genética , Proteínas/genética , Células A549 , Linhagem Celular Tumoral , Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Neoplasias Pulmonares/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas/metabolismo , RNA Mensageiro/genética
2.
Anticancer Res ; 39(9): 4673-4679, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519566

RESUMO

BACKGROUND/AIM: Rats of the adenomatous polyposis coli (Apc)-mutated female polyposis in rat (PIRC) (F344/NTac-Apcam1137) model exhibit a low level of intestinal tumorigenesis and are thus potentially exploitable as a model for identifying substances increasing colorectal cancer (CRC). MATERIALS AND METHODS: To test this possibility, we treated such rats with the bile acid (BA) cholic acid (CA) (0.3% w/w in the diet), known to promote CRC, and assessed tumorigenesis. RESULTS: Precancerous colonic lesions (mucin-depleted foci) and intestinal tumors were dramatically increased in CA-treated rats compared to controls (p<0.01). Colon mucosa proliferation was higher and apoptosis lower than those in controls. Expression of nuclear receptor 1h4 (Nr1h4) gene [encoding for BA receptor farnesoid X receptor (FXR)], organic solute transporter beta (Ostb) and fatty acid-binding protein 6 (Fabp6), FXR-dependent BA transporters, were dramatically down-regulated in CA-treated rats. CONCLUSION: CA-increased tumorigenesis in female PIRC rats, with mechanisms involving increased proliferation, reduced apoptosis and marked down-regulation of genes controlling BA homeostasis. Since BAs have been implicated in CRC, we suggest that female PIRC rats can be used to identify CRC-promoting agents.


Assuntos
Transformação Celular Neoplásica/induzido quimicamente , Ácido Cólico/efeitos adversos , Neoplasias Colorretais/etiologia , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Animais , Apoptose/genética , Proliferação de Células , Modelos Animais de Doenças , Feminino , Expressão Gênica , Genes APC , Mutação , Lesões Pré-Cancerosas , Ratos
3.
Anticancer Res ; 39(8): 4495-4502, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366551

RESUMO

BACKGROUND/AIM: In mice, fetal liver is the first tissue of definitive erythropoiesis for definitive erythroid expansion and maturation. ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in primitive hematopoiesis and T cell development. The aim of this study was to examine whether or not Zfat is involved in definitive erythropoiesis in the fetal liver during mammalian development. MATERIALS AND METHODS: The role of Zfat during mouse fetal erythropoiesis in the fetal liver was examined using tamoxifen-inducible CreERT2 Zfat-deficient mice. RESULTS: Zfat-deficient mice exhibit moderate anemia with small and pale fetal liver through a decreased number of erythroblasts by E12.5. Apoptosis sensitivity in fetal liver erythroid progenitors was enhanced by Zfat-deficiency ex vivo. Moreover, Zfat knockdown partially inhibited CD71-/lowTer119- to CD71highTer119- transition of fetal liver erythroid progenitors with impairment in the elevation of CD71 expression. CONCLUSION: Zfat plays a critical role for erythropoiesis in the fetal liver.


Assuntos
Antígenos CD/genética , Eritropoese/genética , Fígado/crescimento & desenvolvimento , Receptores da Transferrina/genética , Fatores de Transcrição/genética , Animais , Apoptose/genética , Diferenciação Celular/genética , Células Eritroides/metabolismo , Células Eritroides/patologia , Desenvolvimento Fetal/genética , Feto , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Humanos , Fígado/metabolismo , Camundongos , Linfócitos T/citologia , Linfócitos T/metabolismo , Tireoidite Autoimune/genética , Tireoidite Autoimune/patologia
4.
Yonsei Med J ; 60(9): 842-853, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31433582

RESUMO

PURPOSE: Long intergenic non-protein coding RNA 665 (LINC00665) plays a vital role in the development of cancer. Its function in hepatocellular carcinoma (HCC), however, remains largely unknown. MATERIALS AND METHODS: The expressions of LINC00665, miR-186-5p, and MAP4K3 were determined by qRT-PCR. Cell viability and apoptosis were evaluated by MTT and flow cytometry, respectively. Autophagic puncta formation was observed by fluorescence microscopy. Bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation, and RNA pulldown were performed to identify associations among LINC00665, miR-186-5p, and MAP4K3. Western blot was utilized to examine the expressions of MAP4K3, Beclin-1, and LC3. Tumor growth was evaluated in a xenograft model. RESULTS: Elevations in LINC00665 were observed in HCC tissues and cells. The overall survival of HCC patients with high levels of LINC00665 was shorter than those with low levels. In vitro, LINC00665 depletion inhibited viability and induced apoptosis and autophagy. miR-186-5p interacted with LINC00665 and was downregulated in HCC tissues and cells. Upregulation of miR-186-5p inhibited viability and induced apoptosis and autophagy, which were attenuated by upregulation of LINC00665. MAP4K3 was found to possess binding sites with miR-186-5p and was upregulated in HCC tissues and cells. MAP4K3 depletion inhibited viability and induced apoptosis and autophagy, which were attenuated by miR-186-5p inhibitor. In vivo, miR-186-5p expression was negatively correlated with LINC00665 or MAP4K3 in HCC tissues, while LINC00665 was positively correlated with MAP4K3. LINC00665 knockdown suppressed tumor growth. CONCLUSION: LINC00665 was involved in cell viability, apoptosis, and autophagy in HCC via miR-186-5p/MAP4K3 axis, which may provide a new approach for HCC treatment.


Assuntos
Apoptose/genética , Autofagia/genética , Carcinoma Hepatocelular/patologia , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , Adulto , Idoso , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Feminino , Humanos , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases , RNA Longo não Codificante/genética , Regulação para Cima
5.
Cytogenet Genome Res ; 158(4): 205-212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434093

RESUMO

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.


Assuntos
Inativação Gênica , Antígenos de Histocompatibilidade/genética , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Apoptose/genética , Caderinas/biossíntese , Adesão Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/genética
6.
Bioengineered ; 10(1): 306-315, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299871

RESUMO

Long non-coding RNA H19 (H19) is highly expressed in cancers and is considered to highly correlate with the extent of malignant degree. The present study was performed to determine the expression levels of H19 in anaplastic thyroid carcinoma (ATC) tissues and the role of H19 in ATC 8505C cells in vitro and in vivo. Expression of H19 was detected in 19 ATC and 19 normal thyroid tissues by real-time quantitative polymerase chain reaction. Utilizing the siRNA or short hairpin RNA (shRNA) directed against human H19 (H19 siRNA or shRNA H19) depleted H19 in ATC 8505C cells and characterized the outcomes. The results showed that H19 was overexpressed in ATC tissues. Targeting H19 inhibited proliferation, migration, and invasion and induced apoptosis in 8505C cells in vitro and inhibited tumorigenesis and metastasis in vivo. Therefore, the H19 might be an effective target for ATC molecular therapy.


Assuntos
Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Terapia de Alvo Molecular/métodos , RNA Longo não Codificante/genética , Carcinoma Anaplásico da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Animais , Apoptose/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Metástase Linfática , Camundongos , Camundongos Nus , Invasividade Neoplásica , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Carcinoma Anaplásico da Tireoide/metabolismo , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
DNA Cell Biol ; 38(8): 840-848, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31314587

RESUMO

microRNAs are a class of noncoding RNAs that play important roles in cancer progression. microRNA-183-3p (miR-183-3p) is a novel microRNA that is dysregulated in many kinds of cancers. Our previous studies found high expression and oncologic role of high-mobility group nucleosome binding domain 5 (HMGN5) in prostate cancer. In this study, we found that miR-183-3p was downregulated in prostate cancer cells and primary tissues compared with normal controls. In addition, miR-183-3p expression was negatively correlated with HMGN5 expression. On the basis of bioinformatics predication and quantitative polymerase chain reaction and Western blot verification, it is demonstrated that miR-183-3p regulated HMGN5 expression. Luciferase reporter assay confirmed that miR-183-3p directly targeted the 3'-untranslated region of HMGN5. Interestingly, cell proliferation and migration inhibition and apoptosis induction were also observed in miR-183-3p transfected human prostate cancer VCap and C4-2 cells. Moreover, overexpression of HMGN5 significantly reversed the inhibitory effect on cell proliferation and migration and promoted effect on cell apoptosis by miR-183-3p. Our data suggest that dysfunction of miR-183-3p-HMGN5 axis plays an oncogenic role and can be a therapeutic target for prostate cancer.


Assuntos
Proteínas HMGN/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Transativadores/genética , Regiões 3' não Traduzidas , Idoso , Apoptose/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Proteínas HMGN/metabolismo , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Transativadores/metabolismo
8.
Gene ; 714: 143972, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31301483

RESUMO

Among cancers, lung cancer is the most morbidity and mortality disease that is remaining the fatalist. Generally, there are multiple treatment procedures for lung cancer, such as surgery, immunotherapy, radiotherapy and chemotherapy. There is, therefore, an urgent need for more specified and efficient methods for treatment of lung cancer such as RNAi, which in combination with traditional therapies could silence genes that are involved in the drug resistance. These genes may either be motivators of apoptosis inhibition, EMT and DNA repair system promoters or a member of intracellular signaling pathways, such as JAK/STAT, RAS/RAF/MEK, PI3K/AKT, NICD, B-catenin/TCF/LEF and their stimulator receptors including IGFR, EGFR, FGFR, VEGFR, CXCR4, MET, INTEGRINS, NOTCH1 and FRIZZLED, so could be considered as appropriate targets. In current review, the results of multiple studies which have employed drug application after one specific gene silencing or more than one gene from distinct pathways also simultaneous drug and RNAi usage in vitro and in vivo in lung cancer were summarized.


Assuntos
Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/genética , RNA Interferente Pequeno/genética , Animais , Apoptose/genética , Humanos , Transdução de Sinais/genética
9.
Gene ; 714: 143994, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31330233

RESUMO

Long non-coding RNA (lncRNA) potentially regulates tumorigenesis. LncRNA small nucleolar RNA host gene 1 (SNHG1) expression remains high in hepatocellular carcinoma cells; however, its biological mechanism in hepatocellular carcinoma remains unknown. In this study, SNHG1 expression in hepatocellular carcinoma cells was detected by qRT-PCR. Proliferative and migratory potentials of hepatocellular carcinoma cells were determined by CCK-8 and Transwell assay, respectively. Then, the nude mice model of xenograft was employed to verify the effect of SNHG1 on tumor formation in vivo. We identified the potential target of SNHG1 through bioinformatics and dual-luciferase reporter gene. Furthermore, Western blot and RIP assay was used for clarifying their interaction and functions in regulating the development of hepatocellular carcinoma. Our results indicated a high expression of SNHG1 in hepatocellular carcinoma cells. Downregulation of SNHG1 inhibited proliferative and migratory potentials of hepatocellular carcinoma cells in vitro and in vivo. Moreover, the expression of programmed cell death 4 (PDCD4) was positively regulated by SNHG1 through competing with miR-195-5p. These results indicated that SNHG1 participated in the development of hepatocellular carcinoma as a ceRNA to competitively bind to miR-195-5p and thus mediate PDCD4 expression.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Animais , Apoptose/genética , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
10.
Gene ; 714: 143992, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31330234

RESUMO

Increasing studies have demonstrated the important roles of circular RNAs (circRNAs) in human malignancies. Nevertheless, the molecular mechanisms and functions of circRNAs in hepatocellular carcinoma (HCC) are still not fully understood. In the present study, we evaluated circ_0021093 expression in 82 pairs of HCC tissues and 5 cell lines by qRT-PCR. The clinical implications of circ_0021093 were evaluated. In addition, the viability, apoptosis, migration and invasion capacities of different HCC cells were evaluated by gain-/loss-of-function experiments. Target prediction and dual-luciferase reporter experiments were performed to identify the molecular mechanisms of circ_0021093. Upregulation of circ_0021093 was found in HCC tumor samples and cells. Additionally, upregulated circ_0021093 was related to adverse clinical characteristics and an unfavorable prognosis. Furthermore, downregulated circ_0021093 attenuated cell growth, migration and invasion but increased cell apoptosis. By contrast, ectopically expressed circ_0021093 enhanced the abovementioned malignant biological behaviors. For mechanism exploration, circ_0021093 sponges of miR-766-3p were used in HCC cells. In addition, we found that metastasis-associated protein 3 (MTA3) was a direct target of miR-766-3p and that the oncogenic function of circ_0021093 was partly dependent on the miR-766-3p/MTA3 axis according to rescue assays. In conclusion, the circ_0021093/miR-766-3p/MTA3 regulatory axis may be an effective therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , RNA/genética , Apoptose/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Regulação para Cima/genética
11.
Gene ; 714: 143997, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348981

RESUMO

Based on Akt1 and Jak1 key roles in apoptosis and proliferation of many cancers, the aim of this study was to find a new gene therapy strategy by silencing of these main anti-apoptotic genes for HNSCC treatment. Cancerous HN5 and normal HUVEC cell lines were treated with Akt1 and Jak1 siRNAs alone or with each other combined with/without cisplatin. The MTS, flow cytometry, 4',6-diamidino-2-phenylindole staining, real-time PCR and ELISA methods were utilized in this study. The highest percentage of apoptosis was observed in the treatment of Jak1 siRNA/cisplatin group in cancerous HN5 cells (96.5%) where this treatment showed 12.84% apoptosis in normal HUVEC cell line. Cell viability reduced significantly to 64.57% after treatment with Akt1 siRNA in HN5 treated group. Knocking down Akt1 and Jak1 genes using siRNAs could increase levels of apoptosis and reduce proliferation rate in HNSCC indicating the powerful effects of these genes siRNAs with or without chemotherapeutic agents in HNSCC treatment. In conclusion, the combination of siRNA-mediated gene-silencing strategy can be considered as a valuable and safe approach for sensitizing cancer cells to chemotherapeutic agents thus proposed further studies regarding this issue to approve some siRNA based therapeutics for using in clinic.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Neoplasias de Cabeça e Pescoço/genética , Janus Quinase 1/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Cisplatino/farmacologia , Técnicas de Silenciamento de Genes/métodos , Inativação Gênica/efeitos dos fármacos , Inativação Gênica/fisiologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Células Endoteliais da Veia Umbilical Humana , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
12.
Biol Res ; 52(1): 33, 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31255182

RESUMO

BACKGROUND: Studies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long non-coding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. However, its effects on cervical cancer has been kept unknown up to now. The present study was aimed to investigate the relationship between lncRNA CASC11 and cervical cancer and further explore the mechanism of CASC11 effect on cervical cancer progression. MATERIALS: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of CASC11 in cancerous and adjacent normal tissues of patients with cervical cancer as well as in cell lines. The proliferation, migration, invasion and apoptosis were assayed after transfecting the cell with si-CASC11 or pcDNA3.1-CASC11. TOP/FOP-Flash luciferase reporter assay and western blot were used to analysis the activation of Wnt/ß-catenin signaling pathway. Si-CASC11-transfected HeLa cells were subcutaneously inoculated into male athymic (nude) mice to investigate the effect of CASC11 on the tumor formation. RESULTS: We discovered that CASC11, the expression of which was positively associated with the tumor size and the FIGO staging and negatively related to the patients' survival rate, was up-regulated in the cervical cancer tissues and cell lines. Silencing CASC11 inhibited the proliferation, migration as well as invasion and promoted the cell apoptosis. Conversely, overexpression of CASC11 facilitated the cancer cell's proliferation, migration and invasion ability and suppressed the apoptosis. Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/ß-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo. CONCLUSION: Our study demonstrated that CASC11 promoted the cervical cancer progression by activating Wnt/ß-catenin signaling pathway for the first time, which provides a new target or a potential diagnostic biomarker of the treatment for cervical cancer.


Assuntos
Predisposição Genética para Doença , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt/genética , beta Catenina/genética , Animais , Apoptose/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Citometria de Fluxo , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia
13.
Anticancer Res ; 39(7): 3697-3709, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262896

RESUMO

BACKGROUND/AIM: Cervical cancer is considered poorly chemo-sensitive in women and its treatment remains unsatisfactory. Cyperus rotundus is used in Chinese medicine as a therapeutic agent for women's disease. The effects and molecular mechanisms of the ethanol extraction of C. rotundus (CRE) on cervical cancer remain unclear. We aimed to explore the mechanisms and genetic influence of CRE on cervical cancer. MATERIALS AND METHODS: HeLa, human cervical cancer cells were treated with various doses of CRE and changes in cell morphology and cell viability were assessed using microscopy and flow cytometry. Finally, we performed a microarray analysis to scan related genes. RESULTS: The treatment of CRE on HeLa cells caused morphological changes and induced chromatin condensation. DNA microarray analysis showed that CRE led to up-regulation of 449 genes and down-regulation of 484 genes, which were classified in several interaction pathways. CONCLUSION: CRE changed HeLa cell morphology and induced gene expression which associated with apoptosis and cell-cycle arrest. These results provide important information at the transcription level for targeting treatments of human cervical cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Cyperus , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/genética , Apoptose/genética , Ciclo Celular/efeitos dos fármacos , Etanol/química , Feminino , Células HeLa , Humanos , Solventes/química , Neoplasias do Colo do Útero/tratamento farmacológico
14.
BMC Plant Biol ; 19(1): 310, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307401

RESUMO

BACKGROUND: The hypersensitive defense response (HR) in plants is a fast, localized necrotic response around the point of pathogen ingress. HR is usually triggered by a pathogen recognition event mediated by a nucleotide-binding site, leucine-rich repeat (NLR) protein. The autoactive maize NLR gene Rp1-D21 confers a spontaneous HR response in the absence of pathogen recognition. Previous work identified a set of loci associated with variation in the strength of Rp1-D21-induced HR. A polygalacturonase gene homolog, here termed ZmPGH1, was identified as a possible causal gene at one of these loci on chromosome 7. RESULTS: Expression of ZmPGH1 inhibited the HR-inducing activity of both Rp1-D21 and that of another autoactive NLR, RPM1(D505V), in a Nicotiana benthamiana transient expression assay system. Overexpression of ZmPGH1 in a transposon insertion line of maize was associated with suppression of chemically-induced programmed cell death and with suppression of HR induced by Rp1-D21 in maize plants grown in the field. CONCLUSIONS: ZmPGH1 functions as a suppressor of programmed cell death induced by at least two autoactive NLR proteins and by two chemical inducers. These findings deepen our understanding of the control of the HR in plants.


Assuntos
Apoptose/fisiologia , Proteínas de Plantas/fisiologia , Poligalacturonase/fisiologia , Zea mays/fisiologia , Apoptose/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Genes de Plantas , Leucina , Proteínas de Plantas/química , Proteínas de Plantas/genética , Poligalacturonase/química , Poligalacturonase/genética , Recombinação Genética , Sequências Repetitivas de Aminoácidos , Tabaco/genética , Zea mays/enzimologia , Zea mays/genética , Zea mays/imunologia
15.
Zhonghua Zhong Liu Za Zhi ; 41(7): 516-521, 2019 Jul 23.
Artigo em Chinês | MEDLINE | ID: mdl-31357838

RESUMO

Objective: To investigate the effects and mechanisms of miR-144 on proliferation, apoptosis and cisplatin (DDP) resistance of neuroblastoma cells. Methods: Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the mRNA expressions of miR-144 and MYCN in neuroblastoma cell lines, including SH-SY5Y and SK-N-SH, and human umbilical vein endothelial cells HUVEC. The miR-negative control, miR-144 mimics, si-negative control, si-MYCN, miR-144 mimics and pcDNA, miR-144 mimics and pcDNA-MYCN co-transfected SH-SY5Y cells were described as miR-NC, miR-144, si-NC, si-MYCN, miR-144+ pcDNA and miR-144+ pcDNA-MYCN group, respectively. The half maximal inhibitory concentration (IC(50)) and cell proliferation were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The protein expressions of MYCN, p21, cyclin D1, Bax, Bcl-2 were analyzed by western blot. Cell apoptosis was detected by flow cytometry. The cell fluorescence activity was detected by double luciferase reporter gene assay. Results: Compared with HUVEC cells, the expressions of miR-144 in neuroblastoma cells SH-SY5Y and SK-N-SH significantly decreased, while the mRNA and protein expression of MYCN significantly increased. The IC(50) of DDP was 9.16 µg/ml in SH-SY5Y cells. The absorbance value in 490nm (A(490) value) of miR-144 group was 0.30±0.03, significantly lower than 0.46±0.03 of miR-NC group. The cell apoptotic rate of miR-144 group was 26.94%±2.01%, significantly higher than 9.68%±0.52% of miR-NC group. The IC(50) value of DDP in miR-144 group was 2.95±0.26, significantly lower than 9.23±0.61 of miR-NC group. The expressions of p21, cyclin D1, Bax, Bcl-2 in miR-NC and miR-144 group were 2.67±0.19, 0.41±0.04, 2.12±0.21, 0.18±0.01 and 1.01±0.07, 1.00±0.06, 1.00±0.05, 1.00±0.06, respectively, with statistical significance (all P<0.05). Knockdown of MYCN showed the similar effects with those of miR-144 overexpression in SH-SYSY cells. MiR-144 significantly inhibited the fluorescence activity of ectopic MYCN expressing cells and negatively regulated the expression of MYCN. Overexpression of MYCN can reverse the effects of miR-144 on proliferation inhibition, apoptosis promotion and sensitization of SH-SY5Y cells to DDP. Conclusion: MiR-144 inhibits proliferation, promotes apoptosis and enhances the sensitivity of neuroblastoma cells to DDP through targeting MYCN, which provides a potential treatment for neuroblastoma.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Proteína Proto-Oncogênica N-Myc/uso terapêutico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Antineoplásicos/farmacologia , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Criança , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Yonsei Med J ; 60(8): 727-734, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347327

RESUMO

PURPOSE: Hepatocellular carcinoma (HCC) is a common cancer worldwide. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to be aberrantly expressed in hypoxic cancer cells. MALAT1 plays a significant role in many malignancies, including HCC. The aim of this study was to explore the role of MALAT1 in hypoxic HCC cells and its underlying regulatory mechanism. MATERIALS AND METHODS: Quantitative reverse transcription PCR (qRT-PCR) assay was performed to detect the mRNA levels of MALAT1 and microRNA-200a (miR-200a) in HCC cells. Cell invasion and migration ability were evaluated by Transwell assay. Starbase v2.0 and luciferase reporter assay were employed to identify the association between MALAT1 and miR-200a. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. RESULTS: MALAT1 levels were significantly upregulated in HCC cells under hypoxia. Hypoxia promoted proliferation, migration, and invasion, and blocked apoptosis in Hep3B cells, which were weakened by knockdown of MALAT1. Starbase v2.0 showed that MALAT1 and miR-200a have a complementarity region, and luciferase reporter assay verified that MALAT1 interacted with miR-200a in Hep3B cells. Moreover, MALAT1 negatively regulated the expression of miR-200a. miR-200a levels were dramatically downregulated in HCC cells under hypoxia. Upregulation of miR-200a inhibited proliferation, migration, and invasion, and induced apoptosis in Hep3B cells under hypoxia. Interestingly, downregulation of miR-200a partially reversed the tumor-suppressive effect of knockdown of MALAT1 on Hep3B cells in hypoxic condition. CONCLUSION: LncRNA MALAT1 was involved in proliferation, migration, invasion, and apoptosis by interacting with miR-200a in hypoxic Hep3B cells, revealing a new mechanism of MALAT1 involved in hypoxic HCC progression.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Hipóxia Tumoral/genética , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , RNA Longo não Codificante/genética , Regulação para Cima/genética
17.
Int J Oncol ; 55(1): 93-102, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180520

RESUMO

Neuroblastoma (NB) is one of the most common extracranial solid tumors in children, which has complex molecular mechanisms. Increasing evidence has suggested that long noncoding RNAs (lncRNAs) account for NB pathogenesis. However, the function of small nucleolar RNA host gene 16 (SNHG16) in NB is currently unclear. In the present study, publically available data and clinical specimens were employed to verify the expression of SNHG16 in NB. Colony formation, real­time cell proliferation and migration assays were performed to demonstrate the status of cellular proliferation and migration. Flow cytometry was used to examine cell cycle progression in SH­SY5Y cells, and acridine orange/ethidium bromide staining and caspase­3/7 activity measurements were applied to study cell apoptosis. To explore the underlying mechanism of SNHG16 function, an online database was used to identify potential RNA­binding proteins that bind SNHG16. The expression of SNHG16 was revealed to be in line with the clinical staging of NB, and high SNHG16 expression was positively associated with poor clinical outcome. Furthermore, SNHG16 silencing inhibited cell proliferation, repressed migration, and induced cell cycle arrest at the G0/G1 phase in SH­SY5Y cells. Additionally, apoptosis was undetectable in SH­SY5Y cells following SNHG16 silencing. Bioinformatics analysis revealed that SNHG16 regulated cell proliferation in NB through transcriptional and translational pathways. These results suggested that SNHG16 may serve important roles in the development and progression of NB, and could represent a potential target for NB therapy.


Assuntos
Neuroblastoma/genética , RNA Longo não Codificante/genética , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Criança , Pré-Escolar , Inativação Gênica , Humanos , Lactente , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Oncogenes , RNA Longo não Codificante/biossíntese , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Transfecção
18.
Acta Cir Bras ; 34(5): e201900501, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166464

RESUMO

PURPOSE: To analyze the effects of ischemic preconditioning (IPC) in the expression of apoptosis-related genes in rat small intestine subjected to ischemia and reperfusion. METHODS: Thirty anesthetized rats underwent laparotomy and were drive into five groups: control (CG); ischemia (IG); ischemia and reperfusion (IRG); IPC and ischemia (IG+IPC); IPC and ischemia and reperfusion (I/RG+IPC). Intestinal ischemia was performed by clamping the superior mesenteric artery for 60 minutes, whereas reperfusion lasted for 120 minutes. IPC was carried out by one cycle of 5 minutes of ischemia followed by 10 minutes of reperfusion prior to the prolonged 60-minutes-ischemia and 120-minutes-reperfusion. Thereafter, the rats were euthanized and samples of small intestine were processed for histology and gene expression. RESULTS: Histology of myenteric plexus showed a higher presence of neurons presenting pyknotic nuclei and condensed chromatin in the IG and IRG. IG+IPC and I/RG+IPC groups exhibited neurons with preserved volume and nuclei, along with significant up-regulation of the anti-apoptotic protein Bcl2l1 and down-regulation of pro-apoptotic genes. Moreover, Bax/Bcl2 ratio was lower in the groups subjected to IPC, indicating a protective effect of IPC against apoptosis. CONCLUSION: Ischemic preconditioning protect rat small intestine against ischemia/reperfusion injury, reducing morphologic lesions and apoptosis.


Assuntos
Proteínas Reguladoras de Apoptose/análise , Apoptose/genética , Precondicionamento Isquêmico/métodos , Jejuno/irrigação sanguínea , Jejuno/patologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Proteínas Reguladoras de Apoptose/genética , Constrição , Regulação para Baixo , Células Endoteliais/patologia , Expressão Gênica , Masculino , Artéria Mesentérica Superior , Isquemia Mesentérica/genética , Isquemia Mesentérica/patologia , Distribuição Aleatória , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Reprodutibilidade dos Testes
19.
Cell Prolif ; 52(4): e12648, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31199037

RESUMO

OBJECTIVES: Circular RNAs (circRNAs) exist extensively in the eukaryotic genome. The study aimed to identify the role of hsa_circ_0008365 (Circ-SERPINE2) in gastric carcinoma (GC) cells and its downstream mechanisms. MATERIALS AND METHODS: Gene Expression Omnibus (GEO) database was applied to screen differentially expressed circRNAs. CircInteractome, TargetScan and miRecords websites were used to predict target relationships. qRT-PCR and RNase R treatment were utilised to detect molecule expression and confirm the existence of circ-SERPINE2. RNA pull-down assay and dual-luciferase reporter assay were performed for interaction between circRNA and miRNA or mRNA. EdU assay, colony formation assay, and flow cytometry for apoptosis and cell cycle detections were utilised to assess cell function. Western blot and immunohistochemistry (IHC) assays were applied for detection of proteins in tissues or cells. RESULTS: Circ-SERPINE2 and YWHAZ were upregulated, and miR-375 was downregulated in GC tissues and cells. Circ-SERPINE2 and YWHAZ targetedly bound to miR-375. Circ-SERPINE2 promoted cell proliferation and cell cycle progress and inhibited cell apoptosis by sponging miR-375 and regulating YWHAZ expression in vitro. Circ-SERPINE2 repressed solid tumour growth through enhancing miR-375 expression and reducing YWHAZ expression in vivo. CONCLUSIONS: Circ-SERPINE2 is a novel proliferative promoter through the regulation of miR-375/YWHAZ. Circ-SERPINE2/miR-375/YWHAZ axis might provide a novel therapeutic target of GC.


Assuntos
Proteínas 14-3-3/genética , MicroRNAs/genética , Serpina E2/genética , Neoplasias Gástricas/genética , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , RNA , Neoplasias Gástricas/patologia , Regulação para Cima/genética
20.
DNA Cell Biol ; 38(8): 849-856, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31170011

RESUMO

Increasing evidence has suggested the key roles of miRNAs in the initiation and progression of human cancers. miR-383 was downregulated and played a suppressive role in a variety of cancers; however, the function of miR-383 in gastric cancer remains unclear. In this study, we found that the expression of miR-383 was significantly reduced in gastric cancer tissues and correlated with the advanced progression of these cancer patients. Functional analysis showed that overexpression of miR-383 inhibited the proliferation and upregulated the apoptosis of gastric cancer cells. Furthermore, cyclin E2 was predicted as the target of miR-383 using the bioinformatics database. miR-383 bound the 3'-untranslated region of cyclin E2 and decreased the expression of cyclin E2 in gastric cancer cells. Upregulation of cyclin E2 was observed in gastric cancer tissues compared with the normal controls. Highly expressed cyclin E2 was inversely correlated with the level of miR-383 in gastric cancer tissues. Consistent with the decreased expression of cyclin E2 with miR-383, transfection of miR-383 induced cell cycle arrest at G1 phase in gastric cancer cells. Restoration of cyclin E2 significantly reversed the inhibitory effect of miR-183 on gastric cancer cell proliferation. Collectively, our results characterized the suppressive role of miR-383 in gastric cancer partially through targeting cyclin E2.


Assuntos
Ciclinas/genética , MicroRNAs/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Regiões 3' não Traduzidas , Idoso , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Ciclinas/metabolismo , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade
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