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1.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(9): 1143-1148, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31657341

RESUMO

OBJECTIVE: To investigate the regulatory effect of Hippo signaling pathway mediated by large tumor suppressor gene 2 (LATS2) on biological behavior of mice bone marrow mesenchymal stem cells (BMSCs) in vitro. METHODS: BMSCs of C57BL/6 mice were cultured in vitro and passed to the 6th to 7th generations for experiment. BMSCs with activated and inactivated LATS2 were constructed with lentiviral vectors transfections. The BMSCs were allocated to blank control group (MSC group), empty vector control group (MSC-eGFP group), LATS2-overexpressing group (MSC-LATS2 group), empty vector without LATS2 shRNA control group (MSC-shcontrol group) and LATS2-underexpressing group (MSC-shLATS2 group). The transduction efficiencies mediated by the lentiviral vectors were evaluated by flow cytometry. The mRNA and protein expressions of LATS2, phosphorylation of Yes associated protein (p-YAP) and 14-3-3 were quantified by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot respectively. Osteogenic and adipogenic differentiation of BMSCs were evaluated through alizarin red and oil red O staining. Proliferation of BMSCs was evaluated using the CCK-8 assay. The effect of Hippo pathway on horizontal and vertical migration ability of BMSCs was measured by the scratch test and Transwell chamber test. RESULTS: The transduction efficiencies mediated by the lentiviral vectors were 93.1%-97.1%. Compared with MSC-eGFP group, the expressions of LATS2, p-YAP and 14-3-3 in MSC-LATS2 group were significantly elevated [LATS2 mRNA (2-ΔΔCT): 2.55±0.13 vs. 1.08±0.05, LATS2/GAPDH: 2.63±0.11 vs. 1.06±0.08, p-YAP/total YAP: 1.67±0.11 vs. 1.00±0.04, 14-3-3/ß-actin: 2.22±0.20 vs. 0.98±0.06, all P < 0.05], however, compared with MSC-shcontrol group, the expressions in MSC-shLATS2 group were significantly reduced [LATS2 mRNA (2-ΔΔCT): 0.10±0.01 vs. 1.01±0.05, LATS2/GAPDH: 0.09±0.01 vs. 1.05±0.06, p-YAP/total YAP: 0.10±0.02 vs. 1.10±0.09, 14-3-3/ß-actin: 0.05±0.01 vs. 0.90±0.08, all P < 0.05]. It suggested that high and low expression of LATS2 could activate or inhibit Hippo pathway. The osteogenic and adipogenic differentiation and proliferation rate of BMSCs in MSC-LATS2 group were significantly lower than those in MSC-eGFP group, however, those in MSC-shLATS2 group were significantly higher than MSC-shontrol group (all P < 0.05). It suggested that high and low expression of LATS2 could inhibit or promote osteogenesis, adipogenesis and cell proliferation of BMSCs. Scratch test and Transwell chamber test showed that the degree of scratch healing in MSC-LATS2 group was significantly lower than that in MSC-eGFP group [(22.11±3.02)% vs. (45.99±6.58)%], while the number of cells migrating to the subventricular layer of Transwell was significantly reduced (cells/MP: 20.82±3.05 vs. 111.33±13.28, both P < 0.05); the degree of scratch healing in MSC-shLATS2 group was significantly higher than that in MSC-shcontrol group [(70.32±7.17)% vs. (39.28±2.98)%], the number of cells migrating to the subventricular layer of Transwell was increased significantly (cells/MP: 206.19±30.58 vs. 120.10±25.10, both P < 0.05). It suggested that high and low expression of LATS2 could inhibit or promote the horizontal and vertical migration of BMSCs. CONCLUSIONS: LATS2-mediated alteration of Hippo pathway could modulate differentiation, proliferation, and migration of mesenchymal stem cells in vitro.


Assuntos
Células-Tronco Mesenquimais , Animais , Genes Supressores de Tumor , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases , Transdução de Sinais
2.
Anticancer Res ; 39(10): 5449-5459, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570439

RESUMO

BACKGROUND/AIM: Epigenetic abnormalities in microRNAs (miRNAs) have not been analyzed in samples other than pancreaticobiliary tissues in patients with pancreaticobiliary cancer (PBC). To identify miRNAs specific for PBC, the present study analyzed the methylation of tumor-suppressive miRNAs in bile from patients with pancreaticobiliary diseases. MATERIALS AND METHODS: Bile was collected endoscopically or percutaneously from 52 patients with pancreatic cancer, 26 with biliary tract cancer, and 20 with benign pancreaticobiliary diseases. Sequences encoding 16 tumor-suppressive miRNAs were amplified by polymerase chain reaction and sequenced, and their methylation rates were determined. RESULTS: The methylation rates of miR-1247 and miR-200a were significantly higher in patients with pancreatic cancer, and biliary tract cancer than in those with benign diseases, and the methylation rate of miR-200b was significantly higher in patients with pancreatic cancer than in those with benign diseases. CONCLUSION: Methylation of miR-1247, miR-200a, and miR-200b in bile may be useful for distinguishing PBC from benign diseases.


Assuntos
Neoplasias do Sistema Biliar/genética , Metilação de DNA/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Bile/metabolismo , Epigenômica/métodos , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade
3.
Rinsho Ketsueki ; 60(9): 1020-1026, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597823

RESUMO

Fifty years after its discovery, the enigma of monosomy 7 (-7) is eventually unraveling. The key to understanding -7 is "haploinsufficiency" mechanism, through which the function of myeloid tumor-suppressor genes is lost via the deletion/mutation of one allele. In this century, powerful tools such as microarray-CGH and next generation sequencing have enabled the search for tumor-suppressor genes on chromosome 7. Five genes (Samd9, Samd9-like (Samd9L), Ezh2, MLL3, and CUX1) have been identified and their myeloid tumor suppression potential has been verified using mouse models. Mice lacking one Samd9L gene developed MDS at an advanced age, whereas mice children harboring a gain-of-function mutation of Samd9 or Samd9L gene suffer from bone marrow failure, which is frequently followed by childhood MDS with -7, suggesting that these tumor-suppressor genes are the key to understanding not only MDS with -7 but also MDS in general. However, lack of Ezh2 and MLL3, which encode epigenetic regulators, contribute to the promotion of the progression of myeloid tumor cells that harbor abnormalities in the p53 or Ras pathways.


Assuntos
Síndromes Mielodisplásicas/genética , Transtornos Mieloproliferativos/genética , Animais , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Proteínas de Ligação a DNA , Proteína Potenciadora do Homólogo 2 de Zeste , Genes Supressores de Tumor , Proteínas de Homeodomínio , Humanos , Camundongos , Proteínas Nucleares , Proteínas , Proteínas Repressoras , Proteínas Supressoras de Tumor/genética
4.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(4): 378-383, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31512829

RESUMO

OBJECTIVE: To investigate the effect of the long chain non-coding RNA H19 (lncRNA H19) on the invasion and migration of oral cancer cells and its related molecular mechanism. METHODS: The expression levels of lncRNA H19, miR-107, and cyclin-dependent kinase 6 (CDK6) in the immortalized oral epithelial cell line HIOEC and the oral cancer cell line CAL27 were detected by real-time quantitative polymerase chain reaction. CAL27 cells were transfected with siRNA H19, miR-107 mimics, pcDNA H19, or anti-miR-107, and the effects of H19 and miR-107 on the invasion and migration of cells were examined via Transwell assay. The TargetScan database predicted the targeting of H19, miR-107, and CDK6. Double luciferase reporter gene assay was performed to detect interactions among H19, miR-107, and CDK6. Western blot analysis was conducted to examine the effects of H19 and miR-107 on the protein level of the target gene CDK6. RESULTS: Compared with that in HIOEC cells, the expression of H19 was significantly increased in CAL27 cells (P<0.05). After transfection with siRNA H19, the expression of H19 decreased, and the invasion and migration ability of CAL27 cells were inhibited (P<0.05). H19 could bind specifically to the 3'-UTR of miR-107 to modulate the expression of miR-107. Compared with that in HIOEC cells, the expression of miR-107 significantly decreased in CAL27 cells (P<0.05). The expression of miR-107 increased after transfection with siRNA H19, and anti-mir-107 co-transfection could promote the invasion and migration ability of siRNA H19 in CAL27 cells (P<0.05). Compared with that in HIOEC cells, CDK6 expression significantly increased in CAL27 cells (P<0.05), and the expression level of the gene was coregulated by H19 and miR-107 (P<0.05). CONCLUSIONS: lncRNA H19 plays an important role in the development of oral cancer. It can regulate the invasion and migration of oral cancer cells by targeting the miR-107/CDK6 signaling axis.


Assuntos
MicroRNAs , Neoplasias Bucais , RNA Longo não Codificante , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos
5.
Med Oncol ; 36(11): 91, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31560089

RESUMO

The vasoactive intestinal peptide receptor-1(VIPR1) has prominent growth effects on a number of common neoplasms. However, there were contradictions in the effect cross different cancers. We aimed to explore the effect of VIPR1 overexpression on a human lung adenocarcinoma cell line H1299. GEO dataset was used to screen differentially expressed genes in lung adenocarcinoma tissues. The expression of VIPR1 mRNA was determined in the cancer Genome Atlas (TCGA). Immunohistochemical analysis was performed to determine VIPR1 protein expression in lung adenocarcinoma and corresponding adjacent tissues (n = 22). Fluorescence real-time quantitative PCR detected the expression of VIPR1 in human normal lung epithelial cell line BEAS-2B and lung adenocarcinoma cell line H1299. Overexpression strategies were employed to assess functions of VIPR1 expression on several malignant phenotypes in H1299. The expression of VIPR1 was lower in lung adenocarcinoma tissues than that in adjacent tissues. Compared with the normal lung epithelial cells BEAS-2B, VIPR1 was down-regulated in lung cancer cells H1299 (P < 0.05). After the overexpression of VIPR1, we found that VIPR1 significantly inhibited growth, migration, and invasion of H1299 cells (P < 0.05). Our findings point out the tumor suppressor roles of VIPR1 in human LUAD pathogenesis.


Assuntos
Adenocarcinoma de Pulmão/genética , Regulação Neoplásica da Expressão Gênica , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/genética , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/biossíntese , Regulação para Cima
7.
Medicine (Baltimore) ; 98(31): e16685, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374052

RESUMO

The aim of the study was to estimate the prognostic and clinicopathologic significance of miR-125a-5p in human cancers. Eligible studies were obtained from PubMed, Embase, and the Cochrane Library. Combined hazard ratios (HRs) and odds ratios (ORs) were used to evaluate the prognostic and clinicopathologic value of miR-125a-5p. In pan-cancer, high miR-125a-5p expression was associated with better overall survival (OS) (HR = 0.459, 95% confidence interval [CI]: 0.369-0.57, P < .001), and disease-free survival (HR = 0.343, 95% CI: 0.237-0.496, P < .001). Furthermore, favorable OS was also found in lung cancer (HR = 0.343, 95% CI: 0.228-0.517, P < .001) and gastric cancer (HR = 0.341, 95% CI: 0.160-0.725, P = .005) patients with high miR-125a-5p expression. Besides, high miR-125a-5p expression was correlated with early stage (OR = 0.413, 95% CI: 0.228-0.749, P = .004) and negative lymph node metastasis (OR = 0.262, 95% CI: 0.073-0.941, P = .04) in gastric cancer, and was linked with better tumor differentiation in pan-cancer (OR = 1.623, 95% CI: 1.064-2.476, P = .025) and lung cancer (OR = 2.371, 95% CI: 1.358-4.141, P = .002). In conclusion, miR-125a-5p is a tumor suppressor with prognostic and clinicopathologic values for human cancer, and miR-125a-5p overexpression predicted favorable prognosis, early stage, negative lymph node metastasis, and better tumor differentiation. More research should be conducted to test these results.


Assuntos
MicroRNAs/sangue , Neoplasias/sangue , Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Metástase Linfática , Estudos Observacionais como Assunto , Modelos de Riscos Proporcionais
8.
Oncol Rep ; 42(4): 1380-1390, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364737

RESUMO

The dysregulation of microRNAs (miRNAs) is associated with the development and progression of a variety of cancers, including liver cancer. Aberrant expression of miRNA (miR)­124 has been demonstrated in liver cancer, but its functional mechanism in liver cancer is still largely unknown. Metastasis of liver cancer is one of the most common causes of mortality. The present study showed that miR­124 inhibited the proliferation, migration and invasion of liver cancer cells. Furthermore, chloride intracellular channel 1 (CLIC1) was identified as a novel target of miR­124 in liver cancer cells. Overexpression of miR­124 reduced CLIC1 expression at both the protein and mRNA levels in liver cancer cells. Downregulation of CLIC1 decreased the migration and invasion of liver cancer cells without affecting cell proliferation. Taken together, these results showed that CLIC1 is a critical target for miR­124­mediated inhibitory effects on cell migration and invasion. Thus, miR­124 or suppression of CLIC1 may have diagnostic value and therapeutic potential for the treatment of human liver cancer.


Assuntos
Canais de Cloreto/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Movimento Celular/fisiologia , Canais de Cloreto/genética , Progressão da Doença , Regulação para Baixo , Técnicas de Silenciamento de Genes , Genes Supressores de Tumor , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/biossíntese , MicroRNAs/genética , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
9.
Oncol Rep ; 42(4): 1569-1579, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364749

RESUMO

Triple­negative breast cancer (TNBC) is characterized by fast progression with high potential for metastasis, and poor prognosis. The dysregulation of microRNAs (miRNAs) occurring in the initiation or progression of cancers often leads to aberrant gene expression. The aim of the present study was to explore the function of miR­126 in TNBC cells. Expression levels of miR­126­3p were determined by quantitative real­time PCR. Then, the effects of miR­126­3p on migration, proliferation, invasion, and angiogenesis were assessed through in vitro experiments including Cell Counting Kit­8, colony formation, Transwell invasion and vasculogenic mimicry formation assays. One of the target genes for miR­126­3p predicted by TargetScan was confirmed by luciferase activity assay. Results indicated that miR­126­3p expression was reduced in TNBC cell lines. Functional assays revealed that miR­126­3p overexpression inhibited cell proliferation, migration, invasion, colony formation capacity and vasculogenesis by 1.2­, 1.8­, 2.3­, 2.0­ and 3.3­fold, respectively, compared to the miRNA­negative control group of MDA­MB­231 cells (P<0.001, respectively). In addition, the regulator of G­protein signaling 3 (RGS3) was hypothesized and validated as a direct target of miR­126­3p in TNBC. The proliferation, migration, invasion, colony formation capacity and vasculogenesis of MDA­MB­231 cells were significantly increased by 1.4­, 2.0­, 1.8­, 1.4­ and 3.2­fold, respectively, in cells transfected with pcDNA3.0­RGS3 compared to pcDNA3.0­negative control groups (P<0.001, respectively). The influence of miR­126­3p expression was reversed by RGS3 restoration. Collectively, the present study revealed that miR­126­3p plays a role as a tumor suppressor in regulating TNBC cell activities by targeting RGS3, indicating that the miR­126­3p/RGS3 axis may be a potential treatment target.


Assuntos
MicroRNAs/genética , Proteínas RGS/genética , Neoplasias de Mama Triplo Negativas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , MicroRNAs/biossíntese , Invasividade Neoplásica , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Proteínas RGS/biossíntese , Proteínas RGS/metabolismo , Neoplasias de Mama Triplo Negativas/irrigação sanguínea , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
10.
Cell Mol Biol Lett ; 24: 46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31297133

RESUMO

Background: MiR-216a-5p has been reported to be associated with several tumors, including prostate cancer and melanoma. However, its expression level and potential role in esophageal squamous cell carcinoma (ESCC) remain uncertain. Results: Here, we found that miR-216a-5p expression was significantly down-regulated in clinical ESCC tissues and cells. Functional assays were performed to evaluate the biological effects of miR-216a-5p on cell proliferation and cell apoptosis by CCK-8 assay and flow cytometry in ESCC cell lines, EC9706 and TE-9. The results showed that miR-216a-5p overexpression repressed cell proliferation and induced cell apoptosis. Through bioinformatics prediction and luciferase reporter assay, we revealed that miR-216a-5p could directly target tectonic family member 1 (TCTN1). Moreover, TCTN1 was obviously suppressed by miR-216a-5p overexpression. In addition, TCTN1 expression was significantly increased and inversely correlated with the levels of miR-216a-5p in ESCC tissues. More importantly, down-regulation of TCTN1 imitated, while restoration of TCTN reversed the effects of miR-216a-5p on cell proliferation and apoptosis. At the molecular level, we further found that TCTN1 overexpression reversed the effects of miR-216a-5p transfection on the expression of PCNA, Bcl-2 and Bad. Conclusions: Our results demonstrate that miR-216a-5p might serve as a tumor suppressor in ESCC cells through negatively regulating TCTN1 expression, indicating the possibility that miR-216a-5p and TCTN1 might be attractive targets for ESCC therapeutic intervention.


Assuntos
Apoptose , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Proteínas de Membrana/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/fisiopatologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/fisiopatologia , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Transdução de Sinais
11.
Cell Mol Biol Lett ; 24: 48, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333725

RESUMO

Background: In recent years, microRNA-211 (miR211) has been considered as a tumor suppressor in multiple malignancies. However, the function of miR211 in human osteosarcoma has not been explored intensively so far. In this study, the relationship between miR211 and EZRIN was analyzed in human osteosarcoma. Methods: The expression levels of miR211 and EZRIN were measured in both human osteosarcoma cells and tissues. The direct regulatory relationship between miR211 and EZRIN was evaluated using dual-luciferase assay. The effect of miR211 and EZRIN overexpression on cell proliferation, migration/invasion, and apoptosis was detected. Results: The expression of miR211 was obviously lower in osteosarcoma tissues than paracancerous tissues. EZRIN was identified as the direct target of miR211, and up-regulation of miR211 increased the percentage of cell apoptosis, and suppressed cell proliferation as well as cell migration/invasion via directly regulating EZRIN. Conclusions: Our study indicated that miR211 has an important role in the development and progress of osteosarcoma, and it might become a novel target in the diagnosis and treatment of human osteosarcoma.


Assuntos
Apoptose , Neoplasias Ósseas/metabolismo , Proliferação de Células , Proteínas do Citoesqueleto/genética , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Neoplasias Ósseas/fisiopatologia , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , MicroRNAs/genética , Osteossarcoma/fisiopatologia
13.
J Biochem ; 166(5): 433-440, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350893

RESUMO

Nasopharyngeal carcinoma (NPC) is an important type of head and neck malignant cancer with geographical distribution. MicroRNA-449b-5p (miR-449b-5p) is related to the development of various cancers, while its function in NPC remains unknown. The present study aimed to investigate the role and target gene of miR-449b-5p in NPC. Expressions of miR-449b-5p in NPC cell lines and clinical tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was determined by MTT and colony formation assays. Migration and invasion abilities after different treatment were evaluated by wound healing and Transwell assays, respectively. Dual-luciferase reporter assay was performed to explore the relationship between miR-449b-5p and tumour protein D52 (TPD52). TPD52 expression was determined by qRT-PCR and western blot assay. miR-449b-5p was significantly downregulated in NPC cell lines and clinical tissues than the matched control. Overexpression of miR-449b-5p inhibited proliferation, migration and invasion of NPC cells. Dual-luciferase reporter assay indicated that miR-449b-5p directly targeted TPD52. Furthermore, shRNA-mediated downregulation of TPD52 rectified the promotion of cell migration and invasion by miR-449b-5p inhibition. In conclusion, the present study suggests that miR-449b-5p, as a novel tumour-suppressive miRNA against NPC, inhibits proliferation, migration and invasion of NPC cells via inhibiting TPD52 expression.


Assuntos
Movimento Celular/genética , Genes Supressores de Tumor , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia
14.
Biol Res ; 52(1): 35, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296259

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the leading causes of death in the world. NSCLC diagnosed at an early stage can be highly curable with a positive prognosis, but biomarker limitations make it difficult to diagnose lung cancer at an early stage. To identify biomarkers for lung cancer development, we previously focused on the oncogenic roles of transcription factor TFAP2C in lung cancers and revealed the molecular mechanism of several oncogenes in lung tumorigenesis based on TFAP2C-related microarray analysis. RESULTS: In this study, we analyzed microarray data to identify tumor suppressor genes and nine genes downregulated by TFAP2C were screened. Among the nine genes, we focused on growth arrest and DNA-damage-inducible beta (GADD45B) and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) as representative TFAP2C-regulated tumor suppressor genes. It was observed that overexpressed TFAP2C resulted in inhibition of GADD45B and PMAIP1 expressions at both the mRNA and protein levels in NSCLC cells. In addition, downregulation of GADD45B and PMAIP1 by TFAP2C promoted cell proliferation and cell motility, which are closely associated with NSCLC tumorigenesis. CONCLUSION: This study indicates that GADD45B and PMAIP1 could be promising tumor suppressors for NSCLC and might be useful as prognostic markers for use in NSCLC therapy.


Assuntos
Antígenos de Diferenciação/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Neoplasias Pulmonares/genética , Fator de Transcrição AP-2/genética , Biomarcadores Tumorais/análise , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor/fisiologia , Humanos , RNA Mensageiro/análise , RNA Interferente Pequeno/análise
15.
Urologe A ; 58(7): 774-780, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31240374

RESUMO

Due to its low incidence there is only very limited data concerning molecular markers in penile cancer. Recent studies show potential prognostic markers for lymph node metastasis, survival and response to chemotherapy or targeted therapy. Nevertheless the number of patients in the studies is very limited. Therefor clear recommendations for clinical decisions remain very weak. Patients with metastatic disease should be treated in clinical trials with translational biomarker research to improve the molecular tumor board in the future.


Assuntos
Biomarcadores Tumorais/genética , Metástase Linfática/patologia , Terapia de Alvo Molecular , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Prognóstico
16.
J Cancer Res Clin Oncol ; 145(8): 2027-2038, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31243545

RESUMO

BACKGROUND: Increasing evidence has shown that long non-coding RNAs (lncRNAs) are important in hepatocellular carcinoma (HCC) development and progression. In this study, we aim to evaluate the expression of lncRNA FAM99B and its biological function in HCC. METHODS: The expression level of FAM99B in HCC was assessed based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), verified using quantitative real-time polymerase chain reaction (qRT-PCR). HCCLM3 was transfected with lentivirus containing full-length FAM99B to obtain stable overexpressing cell line. Cell Counting Kit 8, clone formation, and transwell assays were used to investigate the effects of FAM99B in HCC progression. In addition, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PANTHER pathway analyses were conducted to investigate the underlying molecular mechanisms. RESULTS: FAM99B was found to be downregulated in HCC tissues compared with adjacent normal tissues based on TCGA, GEO, and qRT-PCR data. Our results revealed that downregulated FAM99B was significantly associated with vascular invasion, advanced histologic grade, and T stage. Kaplan-Meier analysis using TCGA data indicated that decreased FAM99B levels were significantly associated with poor overall survival in patients with HCC. Moreover, overexpression of FAM99B significantly inhibited cell proliferation, migration, and invasion in vitro. Pathway analyses showed that the co-expressed genes of FAM99B mainly participated in the pathways "Metabolic pathways" and "Blood coagulation". CONCLUSION: Our results suggest that FAM99B may serve as a tumor suppressor in HCC and may provide a promising therapy target for patients with HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Hepáticas/patologia , Fígado/metabolismo , RNA Longo não Codificante/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Especificidade de Órgãos/genética , RNA Longo não Codificante/genética , Análise de Sobrevida
17.
Dis Markers ; 2019: 3837687, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182981

RESUMO

This study is aimed at investigating the prognostic biomarkers of patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) and at analyzing the correlation between tumor mutation load (the frequency and number of tumor mutations) and prognosis. Clinical data of 35 patients with stage IIIA-N2 NSCLC were collected from Cancer Hospital, Chinese Academy of Medical Sciences. Whole blood samples from the peripheral vein were taken at different treatment periods, and the mutations of cell-free DNA (cfDNA) were detected. Multivariate analysis showed that smoking (P = 0.0308), mutation number > 2 (P = 0.0283), and max mutation frequency > 0.025 (P = 0.0450) were associated with improved progression-free survival (PFS). The overall survival (OS) of well-differentiated NSCLC patients was better than that of poorly differentiated ones (P = 0.0006). The rates of PFS, disease-free survival, local-regional recurrence-free survival, and local-regional progression-free survival were significantly higher in the group with a mutation number > 2 than in the group with a mutation number ≤ 2. The mutation number of the preoperation group was significantly higher than that of the postradiochemotherapy group (5 vs. 2.5, P = 0.023), and the max mutation frequency change was approximately significant in the postradiochemotherapy group compared with the postoperation group (2.6% vs. 1.85%, P = 0.067). The max mutation frequency is positively correlated with vascular invasion (21.13% vs. 3.62%, P = 0.04). Furthermore, Met, ALK, APC, PTEN, ERBB4, NF1, and other genes, involving multiple tumor suppressor genes and lung cancer-driven genes, did not mutate in recurrence-free patients when compared with recurrent patients. In conclusion, differentiation, smoking, mutation frequency > 0.025, and mutation number > 2 are prognostic factors. The frequency and number of gene mutations in cfDNA are expected to be prognostic predictors of NSCLC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Acúmulo de Mutações , Taxa de Mutação , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Genes Supressores de Tumor , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
18.
Cell Physiol Biochem ; 53(1): 19-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31162914

RESUMO

BACKGROUND/AIMS: Emerging evidence suggests that exosomal microRNAs (miRNAs) mediate hepatoma progression through the post-translational regulation of their targets. However, characteristically-expressed miRNAs and their functions in the tumor and tumor-associated angiogenesis remain poorly understood. METHODS: miRNA sequencing (HiSeq 2500 SE50) was performed to identify miRNA species that are involved in the hepatocellular carcinoma (HCC) pathogenesis. We identified miR-451a downregulation according to its expression and TCGA analysis. miR-451a was found to be mainly involved in cell viability, apoptosis, cell cycle and migration both in HCC and endothelial cell lines. LPIN1 was predicted to be a target of this miRNA based on TargetScan, GSEA analysis, and the Uniprot database. We performed real time PCR and dual luciferase assays to confirm these results. RESULTS: We identified that miR-451a is significantly downregulated in serum-derived exosomes from HCC patients, as compared to expression in those from normal individuals. We further confirmed that overexpression of miR-451a functions in HCC and endothelia cells in vitro and in vivo. Exosomal miR-451a, as a tumor suppressor, was found to induce apoptosis both in HCC cell lines and human umbilical vein endothelial cells (HUVECs). In addition, miR-451a suppressed HUVEC migration, tube formation, and vascular permeability. Importantly, we demonstrated that LPIN1 is a critical target of miR-451a, and promotes apoptosis in both HCC and endothelial cells. CONCLUSION: Our study provides the novel finding that exosomal miR-451a targets LPIN1 to inhibit hepatocellular tumorigenesis by regulating tumor cell apoptosis and angiogenesis. These results have clinical implications regarding the deregulation of miRNAs in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Exossomos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , MicroRNAs/genética , Fosfatidato Fosfatase/genética , Apoptose , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Exossomos/patologia , Genes Supressores de Tumor , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/patologia
19.
Cancer Res ; 79(12): 3028-3030, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31201165

RESUMO

Advances in high-throughput genomic and epigenomic technologies have revealed the tremendous complexity of the transcriptional landscape. Beyond protein-coding RNAs (derived from only ∼1.5% of the genome), noncoding RNAs (ncRNA) are emerging as versatile key regulators of gene information involved in multiple major biological processes. Accordingly, deregulation of ncRNA expression has been associated with multiple diseases, including cancer. In this issue of Cancer Research, Shahabi and colleagues characterize LINC00261 as a tumor suppressor long ncRNA epigenetically silenced in lung cancer. They provide crucial mechanistic insights to explain its role in lung tumorigenesis, demonstrating that deregulation of the LINC00261/FOXA2 locus disrupts DNA damage repair signaling, cell-cycle control, and cell proliferation.See related article by Shahabi et al., p. 3050.


Assuntos
Neoplasias Pulmonares/genética , RNA Longo não Codificante/genética , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Genes Supressores de Tumor , Humanos
20.
Nat Methods ; 16(6): 505-507, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31110280

RESUMO

Tumors from individuals with cancer are frequently genetically profiled for information about the driving forces behind the disease. We present the CancerMine resource, a text-mined and routinely updated database of drivers, oncogenes and tumor suppressors in different types of cancer. All data are available online ( http://bionlp.bcgsc.ca/cancermine ) and downloadable under a Creative Commons Zero license for ease of use.


Assuntos
Mineração de Dados/métodos , Bases de Dados Factuais , Genes Supressores de Tumor , Neoplasias/genética , Oncogenes , Publicações Periódicas como Assunto , Software , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos
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