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1.
Gene ; 7242020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30898706

RESUMO

AIM: The long noncoding RNAs (lncRNAs) have gradually been reported to be an important class of RNAs with pivotal roles in the development and progression of myocardial infarction (MI). In this study, we hypothesized that genetic variant of cyclin-dependent kinase inhibitor 2B antisense RNA (ANRIL) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) may affect the prognosis of MI patients. METHODS: The study included 401 Han Chinese MI patients and 409 controls. Four lncRNA tag single nucleotide polymorphisms (SNPs)-ANRIL rs9632884 and rs1537373, MALAT1 rs619586 and rs3200401-were selected. SNP genotyping was performed by an improved multiplex ligation detection reaction assay. RESULTS: rs9632884 and rs3200401 SNPs were significantly associated with lipid levels in both controls and MI patients (P < 0.003-0.046). Several SNPs interacted with sex and age to modify total cholesterol, low-density lipoprotein cholesterol, and creatinine levels to modify the risk of MI. No association between the lncRNAs SNPs and susceptibility to MI was found (P > 0.05 for all). CONCLUSIONS: Taken together, this study provides additional evidence that genetic variation of the ANRIL rs9632884 and MALAT1 rs3200401 can mediate lipid levels in MI patients.


Assuntos
Colesterol/sangue , Infarto do Miocárdio/genética , RNA Longo não Codificante/genética , Triglicerídeos/sangue , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Colesterol/genética , Doença da Artéria Coronariana/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Polimorfismo de Nucleotídeo Único , Fumar/genética , Triglicerídeos/genética
2.
Gene ; 723: 144126, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589963

RESUMO

Non-coding RNAs are known to participate in cancer initiation, progression, and metastasis by regulating the status of chromatin epigenetics and gene expression. Although these non-coding RNAs do not possess defined protein-coding potential, they are involved in the expression and stability of messenger RNA (mRNA). The length of microRNAs (miRs) ranges between 20 and 22 nt, whereas, long non-coding RNAs (lncRNAs) length ranges between 200 nt to 1 Kb. In the case of circular RNAs (circRNAs), the size varies depending upon the length of the exon from where they were derived. Epigenetic regulations of miR and lncRNA genes will influence the gene expression by modulating histone acetylation and methylation patterns. Especially, lncRNAs will act as a scaffold for various epigenetic proteins, such as EZH2 and LSD1, and influence the chromatin epigenetic state at various genomic loci involved at silencing. Thus investigations on the expression of lncRNAs and designing drugs to modulate the expression of these genes will have a profound impact on future therapeutics against cancers such as Glioblastoma Multiforme (GBM) and also against various other diseases. With the recent advancements in genome-wide transcriptomic studies, scientists are focused on the non-coding RNAs and their regulations on various cellular processes involved in GBM and on other types of cancer as well as trying to understand possible epigenetic modulations that help in generating promising therapeutics for the future generations. In this review, the involvement of epigenetic proteins, enzymes that change chromatin architecture and epigenetic landscape and new roles of lncRNAs that are involved in GBM progression are elaborately discussed.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , MicroRNAs/genética , RNA Longo não Codificante/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/genética , Ensaios Clínicos como Assunto , Epigênese Genética/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Glioblastoma/genética , Humanos
3.
J Environ Pathol Toxicol Oncol ; 38(2): 119-131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679275

RESUMO

BACKGROUND/AIMS: LncRNAs are significant regulators in multiple cancers including hepatocellular carcinoma (HCC). Recently, lncRNA ANRIL has been reported to be elevated during multiple cancer types, exhibiting oncogenic roles. However, the exact biological mechanism of ANRIL is still poorly understood in HCC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assays were utilized to detect expressions of ANRIL, miR-384, and STAT3. CCK8 and EDU assays were employed to evaluate HCC cell proliferation. A flow cytometry assay was used to detect the HCC cell cycle and cell apoptosis. The scratch migration and Transwell invasion assays were performed to test cell migration and invasion, respectively. RIP and RNA pull-down assays were carried out to confirm the correlation between ANRIL and miR-384. The dual-luciferase reporter assay was used to prove the association between miR-384 and STAT3. Western blotting analysis was performed to examine protein levels of STAT3. IHC and HE staining were employed to detect Ki-67 and histopathology. RESULTS: ANRIL expression was upregulated in HCC cells, including SMCC7721, HepG2, MHCC-97H, SNU449 and HUH-7 cells, in comparison to the normal human liver cells LO2. Knockdown of ANRIL suppressed HCC cell proliferation and induced cell cycle arrest and apoptosis. HCC cell migration and invasion capacity were inhibited by inhibition of ANRIL. Bioinformatics analyses revealed that ANRIL could interact with miR-384. miR-384 was significantly decreased in HCC cells, and overexpression of miR-384 repressed HCC progression. STAT3 was predicted as a target of miR-384, and miR-384 can modulate STAT3 levels negatively in vitro. ANRIL can suppress HCC development through regulating miR-384 and STAT3 in vivo. CONCLUSION: ANRIL is involved in HCC progression by direct targeting of miR-384 and STAT3. Also, ANRIL could act as a potential candidate for HCC diagnosis, prognosis, and therapy.


Assuntos
Carcinogênese/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/genética , Carcinoma Hepatocelular/fisiopatologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Progressão da Doença , Células HEK293 , Células Hep G2 , Humanos , Neoplasias Hepáticas/fisiopatologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo
4.
Medicine (Baltimore) ; 98(45): e17583, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702614

RESUMO

BACKGROUND: Long noncoding RNA paternally expressed 10 (lncRNA PEG10) is highly expressed in a variety of human cancers and related to the clinical prognosis of patients. However, to date there has been no previous study evaluating the prognostic significance of lncRNA PEG10 in gliomas. In the present study, we investigated the expression levels of lncRNA PEG10 to determine the prognostic value of this oncogene in human gliomas. METHODS: Expression levels of lncRNA PEG10 were detected by real-time polymerase chain reaction in a hospital-based study cohort of 147 glioma patients and 23 cases of patients with craniocerebral trauma tissues. Associations of lncRNA PEG10 expression with clinicopathological variables and clinical outcome of glioma patients were investigated. RESULTS: The results indicated that expression levels of lncRNA PEG10 were significantly increased in human gliomas compared to normal control brain tissues. In addition, lncRNA PEG10 expression was progressively increased from pathologic grade I to IV (P = .009) and correlated with the Karnofsky performance status (P = .018) in glioma patients. Furthermore, we also found that glioma patients with increased expression of lncRNA PEG10 had a higher risk to relapse and a statistically significant shorter overall survival (OS) than patients with reduced expression of lncRNA PEG10. In multivariate analysis, expression level of lncRNA PEG10 was found to be an independent prognostic factor for both progression-free survival and OS in glioma patients. CONCLUSIONS: LncRNA PEG10 served as an oncogene and played crucial roles in the progression of glioma. Molecular therapy targeted on lncRNA PEG10 might bring significant benefits to the clinical outcome of malignant glioma.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , RNA Longo não Codificante/genética , Regulação para Cima , Adulto , Idoso , Neoplasias Encefálicas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Análise de Sobrevida , Adulto Jovem
5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 832-837, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750827

RESUMO

Objective To investigate the relationship between long-chain intergenic non-coding RNA324 (LINC00324) and immunophenotype in peripheral blood leukocytes of acute myeloid leukemia (AML) patients. Methods Real-time quantitative PCR and bioinformatics databases were utilized to analyze the expression level of LINC00324 in peripheral blood leukocytes and cell lines KG-1, THP-1 and U937 in AML patients. The relationships of the expression level of LINC00324 with the red blood cell and platelet count, the expression levels of LINC00324 and immunophenotypes in 40 AML patients were analyzed by Person correlation analysis. The immunophenotypes included CD14, CD68, CD64, CD11b, CD4, CD45, CD33, HLA-DR, CD163, CD2, CD58, CD117, CD43, CD34, CD99, CD8, CD38, CD10, CD13, CD56, CD7, TdT, CD235a, CD138, CD61, MPO and CD19. Simultaneously, the cBioPortal database datasets (TCGA, NEJM 2013) were used to analyze the clinical characteristics of 173 AML patients, and to analyze the correlations between the expression level of LINC00324 and the peripheral blood blast percentage and white blood cell count in tumor samples. Results The expression of LINC00324 in peripheral blood leukocytes of AML patients was down-regulated, and its expression level was significantly correlated with immunophenotype CD33, red blood cell and platelet count. Analysis of bioinformatics database showed that LINC00324 was under-expressed in myeloid leukemia cell lines. The expression of LINC00324 in AML patients was associated with multiple immunophenotypes such as CD33, CD117, CD11b, CD14 and CD64 and was negatively correlated with peripheral blood blast percentage and white blood cell count. Conclusion LINC00324 may be involved in regulating the differentiation, development and function of immune cells, which providing a new strategy for the development of targeted drugs or treatment of AML.


Assuntos
Imunofenotipagem , Leucemia Mieloide Aguda/classificação , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Antígenos HLA-DR , Humanos , Contagem de Leucócitos , Leucócitos/metabolismo
6.
Neoplasma ; 66(6): 954-962, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31607132

RESUMO

Non-small cell lung cancer (NSCLC) is the most prevalent subtype of lung cancer histologically, and an increasing number of evidences have shown during the past years that long non-coding RNAs (lncRNAs) are involved in tumorigenesis. Here we found a long non-coding RNA, GATA2-AS1, repressing NSCLC cells proliferation via regulating GATA2. GATA2-AS1 gene is located at antisense strand of GATA2 on chromosome while GATA2-AS1 RNA interacts with GATA1 protein at promoter region of GATA2 and then inhibits its transcription. Moreover, GATA2-AS1 is transcriptionally repressed by MYC in NSCLC cells. To conclude, our study discovered the role of lncRNA GATA2-AS1 in human non-small cell lung cancer growth thus providing a potential target for lung cancer drugs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Fator de Transcrição GATA2/genética , Neoplasias Pulmonares/genética , RNA Longo não Codificante/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-myc/genética
7.
Medicine (Baltimore) ; 98(40): e17276, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577719

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer in adults, and patients with advanced ccRCC have a 5-year survival rate of <30%. The poor prognosis of ccRCC is closely related to its lacking of potential therapeutic and prognostic biomarkers. This meta-analysis aimed to elucidate the precise prognostic value of long non-coding RNAs (lncRNAs) in patients with ccRCC. METHODS: A literature search was performed in related databases up to January 31, 2019. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to explore the relationship between special lncRNAs expression and survival in patients with ccRCC. RESULTS: After literature researching, a total of 16 studies, including 13 lncRNAs were identified. The data from studies that investigated the association between lncRNA expression and survival outcomes in patients with ccRCC were extracted. Results revealed that lncRNAs expression was significantly associated with poor overall survival (OS) outcome in patients with ccRCC (HR = 1.71, 95%CI = 1.40-2.01 in up-regulated subgroup; HR = 0.53, 95% CI = 0.25-0.80 in down-regulated subgroup). The overexpression of PVT1 was significantly associated with poor OS in ccRCC (HR = 1.51, 95% CI = 1.02-2.00). Meanwhile, up-regulation of LUCAT1 was significantly related to worse OS in ccRCC patients (HR = 1.51, 95% CI = 1.01-2.00). CONCLUSIONS: These results suggest that lncRNAs could be used to predict unfavorable prognosis and function as potential prognostic biomarkers in ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , RNA Longo não Codificante/genética , Fatores Etários , Biomarcadores Tumorais , Carcinoma de Células Renais/patologia , Proliferação de Células , Ensaios Clínicos como Assunto , Regulação para Baixo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fatores Sexuais , Taxa de Sobrevida , Carga Tumoral , Regulação para Cima
8.
Medicine (Baltimore) ; 98(42): e17412, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626095

RESUMO

BACKGROUND: Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is a 1752-bp lncRNA transcribed from m8q24 genomic region. A lot of investigations have confirmed the involvement of CCAT2 in the tumorigenesis of many cancer types. Previous studies found that over-expression of CCAT2 significantly promoted cell migration and proliferation, and inhibited apoptosis of HCC cells. In the present investigation, the clinical value and prognostic significance of CCAT2 were investigated. METHODS: The 122 pairs of HCC tissues and adjacent normal liver tissues were acquired between September 2013 and February 2018. The expression levels of CCAT2 in HCC tissues and their corresponding adjacent normal liver tissues were examined by RT-qPCR analysis. Survival was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent prognostic indicators were determined in the multivariate analysis using Cox's proportional hazard model. RESULTS: CCAT2 expression levels were significantly increased in HCC tissues compared to that in their normal counterparts (P < .001). CCAT2 expression was significantly correlated with vascular invasion (P = .001), histopathologic grading (P = .001), distant metastasis (P = .002) and TNM stage (P = .018). A Kaplan-Meier survival curve showed that the overall survival rate of HCC patients in high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = .016). In addition, COX multivariate analysis showed that high expression of CCAT2 was an independent risk factor for predicting shorter overall survival time in HCC (HR = 2.126, 95%CI:1.273-8.775, P = .021). CONCLUSIONS: Taken together, this research revealed that lncRNA CCAT2 may serve as a potential biomarker for predicting overall survival time in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/genética
9.
Life Sci ; 236: 116918, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610208

RESUMO

Long noncoding RNAs (lncRNAs) are characterized as a group of endogenous RNAs that are more than 200 nucleotides in length and have no protein-encoding function. More and more evidence indicates that lncRNAs play vital roles in various human diseases, especially in tumorigenesis. Focally amplified lncRNA on chromosome 1 (FAL1), a novel lncRNA with enhancer-like activity, has been identified as an oncogene in multiple cancers and high expression level of FAL1 is usually associated with poor prognosis. Dysregulation of FAL1 has been shown to promote the proliferation and metastasis of cancer cells. In the present review, we summarized and illustrated the functions and underlying molecular mechanisms of FAL1 in the occurrence and development of different cancers and other diseases. FAL1 has the potential to appear as a feasible diagnostic and prognostic tool and new therapeutic target for cancer patients though further investigation is needed so as to accelerate clinical application.


Assuntos
Carcinogênese/genética , Carcinogênese/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Neoplasias/patologia , RNA Longo não Codificante/genética , Humanos , Transdução de Sinais
10.
Life Sci ; 236: 116906, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614147

RESUMO

AIMS: The anti-hyperglycemic action of metformin on skeletal muscles is presently unclear. Long noncoding RNAs (lncRNAs) are implicated in multiple cellular functions. This study aims to explore the role of lncRNAs in the glucometabolic action of metformin on skeletal muscle cells. MAIN METHODS: Metformin accumulation was assessed using [14C]-metformin. A lncRNA array was used to investigate metformin-regulated lncRNAs in C2C12 skeletal muscle cells. Knockdown studies were applied to evaluate the function of lncRNA Dreh. A colorimetric assay was used for the measurement of medium glucose concentration; glucose transport was assessed using [3H]-2-deoxyglucose; real-time PCR was used for RNA expression analysis, and western blotting was used to assess protein expression in myotubes. A Dreh overexpression plasmid was transfected into the cells. KEY FINDINGS: Metformin accumulated in C2C12 myotubes. Metformin reduced medium glucose concentration and repressed lncRNA Dreh expression in the myotubes. Knockdown of Dreh in the myotubes resulted in reduced glucose concentration in the culture medium, increased glucose transport, and increased levels of GLUT4 protein in the plasma membrane. Overexpression of Dreh attenuated the glucose-lowering effect of metformin in myotubes. SIGNIFICANCE: The glucoregulatory actions of metformin are mediated in part by a lncRNA, Dreh, in the skeletal muscle cells. Dreh is a novel regulator for glucose transport and could be a therapeutic target for diabetes.


Assuntos
Glucose/metabolismo , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , RNA Longo não Codificante/genética , Animais , Transporte Biológico , Linhagem Celular , Regulação da Expressão Gênica , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Camundongos , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1515-1521, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607306

RESUMO

OBJECTIVE: To investigate the expression and significance of LncRNA RP11-513G11.1 in peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL), and to analyze its correlation with clinicopathological features and prognosis of patients. METHODS: The serum samples of 93 patients with DLBCL(DLBCL group) and 62 normal persons (control group) were collected from the Department of Hematology, Southwest Medical University. The expression of RP11-513G11.1 in serum samples was detected by real-time fluorescence quantitative PCR, the relationship between the RP11-513G11.1 expression with clinicopathological characteristics and prognosis was analyzed. RESULTS: Compared with normal control group, the expression of RP11-513G11.1 significantly increased in DLBCL patients (P<0.001). The expression of RP11-513G11.1 not related with the age, sex, course of treatment and germinal center B-cell-like lymphoma(GCB) subtypes of the patients, but it related with the diameter of tumor,Ann Arbor stage,B symptoms,chemosensitivity and the international prognostic index(IPI) (P<0.05). The progression-free survival time and overall survival time of patients, whom with high expression of RP11-513G11.1 were significantly shorter than those of RP11-513G11.1 low expression(P<0.001). The median progression-free survival time and overall survival time of chemotherapy-sensitive patients were significantly longer than those of chemotherapy-resistant patients (P<0.001). Univariate analysis and multivariate Cox regression analysis showed that Ann Arbor stage, RP11-513G11.1 expression, IPI and chemosensitivity were also the independent factors affecting the prognosis of DLBCL patients(P<0.05). CONCLUSION: RP11-513G11.1 is highly expressed in patients with DLBCL, which is related with the prognosis of DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B , Linfócitos B , Centro Germinativo , Humanos , Linfoma Difuso de Grandes Células B/genética , Prognóstico , RNA Longo não Codificante/genética
12.
Anticancer Res ; 39(10): 5381-5391, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570433

RESUMO

BACKGROUND/AIM: Long noncoding RNAs (lncRNAs) are noncoding transcripts that are >200 nucleotides in length. However, the biological functions and regulation mechanisms of lncRNAs in gastric carcinogenesis remain unknown. MATERIALS AND METHODS: The expression levels of Linc00472 were analyzed by real-time PCR. The DNA methylation status was assessed using Combined Bisulfite Restriction Analysis (COBRA). The biological role of Linc00472 was assessed in AGS cells with Linc00472 overexpression. RESULTS: Using the next-generation sequencing approach, we identified DNA methylation-associated lncRNAs in gastric cancer cells. Among them, the expression level of Linc00472 significantly decreased in gastric cancer tissues compared to adjacent normal tissues. Furthermore, we observed a more frequent hypermethylation of CpG islands upstream of Linc00472 in gastric cancer tissues. Ectopic Linc00472 expression could significantly inhibit gastric cancer cell growth and migration. CONCLUSION: Epigenetically regulated Linc00472 expression plays a crucial role in modulating gastric cancer cell growth and motility.


Assuntos
Metilação de DNA/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ilhas de CpG/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos
13.
Life Sci ; 237: 116904, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606380

RESUMO

AIMS: Long non-coding RNAs (LncRNAs) play central roles in the formation and development of gastric cancer (GC). The aim of this study was to evaluate the expression of PURPL and NONHSAT062994 and the relationship between their expressions with clinical characteristics in GC. MAIN METHODS: PURPL and NONHSAT062994 LncRNAs and p53 gene expression levels were analyzed both in 50 pairs of cancerous and adjacent noncancerous tissue samples in GC patients using qRT-PCR and in four sets of data obtained from Gene Expression Omnibus (GEO) database. Chi-square (χ2) test was used to determine the relationship between PURPL, NONHSAT062994 RNA levels and the clinicopathological characteristics of GC. Receiver operating characteristic (ROC) curves were drawn to represent sensitivity and specificity of PURPL and NONHSAT062994 expression as markers of GC. KEY FINDINGS: Expression of PURPL was significantly upregulated in 50 GC samples as well as in GC tissues from GSE13911 and GSE27342 datasets. Our results demonstrated that PURPL RNA level in GC was significantly related to tumor size and histopathological grade. p53 expression at both protein and mRNA levels were significantly decreased in GC tissues compared to adjacent control samples. NONHSAT062994 expression was downregulated in 50-pair GC and GC tissues from GSE13915 dataset. However, NONHSAT062994 showed no consistently differential expression in GSE2637dataset. NONHSAT062994 was significantly associated with histological grade and tumor size. SIGNIFICANCE: Overall, these results suggest that PURPL and NONHSAT062994 may play critical roles in the progression of GC and therefore might be considered as candidate tumor markers for therapeutic goals.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Estudos de Casos e Controles , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Células Tumorais Cultivadas
14.
Life Sci ; 237: 116902, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610195

RESUMO

AIMS: Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) promotes hepatic stellate cell (HSC) autophagy and activation. However, the underlying mechanism remains unknown. Noncoding RNAs (ncRNAs) including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have received increasing attention. We aimed to investigate the roles of the lncRNA nuclear enriched abundant transcript 1 (NEAT1), miR-29b, and autophagy related protein 9a (Atg9a), and their relationships with each other during IGFBPrP1-induced HSC autophagy and activation. MAIN METHODS: Levels of NEAT1, miR-29b, Atg9a, and autophagy were detected in adenovirus-mediated IGFBPrP1 (AdIGFBPrP1)-treated mouse liver tissue and immortalized mouse hepatic stellate cell line JS1 transfected with either AdIGFBPrP1 or siIGFBPrP1. In AdIGFBPrP1-treated JS1 cells, autophagy and activation were detected after altering NEAT1, miR-29b, or Atg9a levels. In AdIGFBPrP1-treated JS1 cells, relationships among NEAT1, miR-29b, and Atg9a were explored using dual-luciferase reporter assays, Western blot, qRT-PCR, and immunofluorescence. KEY FINDINGS: IGFBPrP1 increased levels of NEAT1, Atg9a, and autophagy while decreasing the level of miR-29b in mouse liver tissues and mouse HSCs. Moreover, NEAT1 increased HSC autophagy and activation while miR-29b decreased both processes. Atg9a also participated in IGFBPrP1-induced HSC autophagy and activation. Importantly, NEAT1, miR-29b, and Atg9a formed a NEAT1/miR-29b/Atg9a regulatory axis for IGFBPrP1-induced HSC autophagy and activation. SIGNIFICANCE: Our study unveiled the new NEAT1/miR-29b/Atg9a regulatory axis involved in IGFBPrP1-induced mouse HSC autophagy and activation. The study thus provides new insights in the pathogenesis and potential therapeutic strategies of liver fibrosis.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Autofagia , Células Estreladas do Fígado/patologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Cirrose Hepática/patologia , Proteínas de Membrana/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas de Transporte Vesicular/metabolismo , Adenoviridae/genética , Animais , Proteínas Relacionadas à Autofagia/genética , Células Cultivadas , Células Estreladas do Fígado/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Transporte Vesicular/genética
15.
Life Sci ; 237: 116929, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610210

RESUMO

LncRNA small nucleolar RNA host gene 3 (Snhg3) has been involved in cell proliferation and migration in malignant cells. However, its role in regulating functions of non-malignant cells has been hardly reported. Here, we found Snhg3 expression was sharply induced in primary brain microvascular endothelial cells (BMVECs) treated with oxygen-and-glucose-deprivation (OGD) plus hemin, an in vitro model of intracerebral hemorrhage (ICH). Downregulation of Snhg3 by siRNA transfection improved cell proliferation and migration abilities and reduced cell apoptosis and monolayer permeability in BMVECs under treatment with OGD plus hemin. Snhg3 overexpression suppressed cell proliferation and migration and increased cell apoptosis and monolayer permeability under normal condition. In ICH rats, downregulation of Snhg3 by siRNA injection improved behavioral and histological manifestations, including number of right turns, limb placement score, integrity of blood-brain barrier (BBB), brain water content and cell apoptosis in vivo. In the mechanism exploration, we found that, TWEAK and Snhg3 displayed a positive correlation with each other. Snhg3 overexpression increased expression of TWEAK protein and its receptor Fn14, that were also induced by OGD plus hemin, activating the downstream neuroinflammatory pathway STAT3 and enhancing the secretion of MMP-2/9. Finally, the TWEAK-siRNA, the Fn14 inhibitor ATA and the STAT3 blocker AG490 were respectively used to treat BMVECs under treatment with OGD plus hemin. Our results showed either TWEAK downregulation, Fn14 inhibition, or STAT3 blockade, could rescue Snhg3-induced impairment of BMVEC functions. In conclusion, the lncRNA Snhg3 contributes to dysfunction of cerebral microvascular cells in ICH rats by activating the TWEAK/Fn14/STAT3 pathway.


Assuntos
Encéfalo/patologia , Hemorragia Cerebral/patologia , Citocina TWEAK/metabolismo , Endotélio Vascular/patologia , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Receptor de TWEAK/metabolismo , Animais , Comportamento Animal , Encéfalo/metabolismo , Células Cultivadas , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Circulação Cerebrovascular/fisiologia , Citocina TWEAK/genética , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Masculino , Microvasos/metabolismo , Microvasos/patologia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/genética , Receptor de TWEAK/genética , Cicatrização
16.
Gene ; 721: 144093, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31473323

RESUMO

Previous studies have determined that long non-coding RNA (lncRNA) Fer-1-like protein 4 (FER1L4) is suppressed in osteosarcoma (OS) and inhibits the tumorigenesis in a variety of cancer. However, the precise biological of FER1L4 in OS has not been cleared. The aim of this study is to investigate the roles and potential mechanisms of FER1L4 in apoptosis and epithelial-mesenchymal transition (EMT) in OS. In the present study, the levels of FER1L4 were decreased significantly in OS tissues and cell lines compared with non-tumorous tissues or hFOB1.19. Knockdown of FER1L4 in OS cells decreased the apoptosis rate, but increased the OS cell proliferation, upregulated the expression levels of CD133 and Nanog, as well as promoted Twist1 expression, increased the N-cadherin and Vimentin expression. In turn, the opposite trends were observed upon overexpression of FER1L4. In addition, the expression of PI3K, p-AKT (Ser470) and p-AKT (Thr308) was upregulated by siFER1L4, while decreased upon overexpression of FER1L4. MicroRNA (miRNA) -18a-5p, an osteosarcoma-promoting miRNA which was suggested a target of FER1L4 in osteosarcoma, was identified to be a functional target of FER1L4 on the regulating of cell apoptosis and EMT, presently. The effects of FER1L4 overexpression on the markers of cell apoptosis, proliferation, EMT, and stemness and PI3K/AKT signaling were all reversed by miR-18a-5p upregulation. Furthermore, the suppressor of cytokine signaling 5 (SOCS5) was confirmed a target gene of miR-18a-5p by luciferase gene reporter assay and SOCS5 suppression by miR-18a-5p attenuated the effects of FER1L4 overexpression on the OS cells apoptosis and the expressed levels of PI3K, AKT, Twist1, N-cadherin and Vimentin. In conclusion, our data indicated thatthe overexpression of FER1L4 promoted apoptosis and inhibited the EMT markers expression and PI3K/AKT signaling pathway activation in OS cells via downregulating miR-18a-5p to promote SOCS5.


Assuntos
Apoptose , Neoplasias Ósseas/metabolismo , Transição Epitelial-Mesenquimal , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Proteínas Supressoras da Sinalização de Citocina/genética
18.
Cell Biochem Funct ; 37(7): 525-533, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31478234

RESUMO

Increasing evidence has indicated the important roles of long noncoding RNA small nucleolar RNA host gene 7 (SNHG7) in tumourigenesis as a potential oncogene. However, the function of SNHG7 in hepatic carcinoma remains unclear. In the present study, we found that SNHG7 expression was significantly upregulated in hepatic carcinoma tissues, especially in aggressive cases, and it was closely correlated with the poor prognosis. Furthermore, knockdown of SNHG7 inhibited the proliferation, migration, and invasion of hepatic carcinoma cell lines in vitro. Mechanistically, SNHG7 directly interacted with miR-425 as a ceRNA. Moreover, knockdown of SNHG7 significantly inhibited the tumorigenic Wnt/ß-catenin/EMT pathway. SNHG7 regulated Wnt/ß-catenin/EMT pathway through sponging miR-425 and played an oncogenic role in hepatic carcinoma progression. Together, our study elucidated the role of SNHG7 as a ceRNA in hepatic carcinoma, provided new potential diagnosis and therapeutic application in hepatic carcinoma progression. SIGNIFICANCE OF THE STUDY: SNHG7 could promote proliferation and metastasis of hepatic carcinoma cell in vitro and in vivo, suggesting that SNHG7 exerts tumorigenic role in hepatic carcinoma progression. Further mechanism research revealed that SNHG7 exhibited the tumorigenic role through Wnt/ß-catenin/EMT pathway as a miR-425 sponge. These findings provided new cues to understand the molecular signalling network in carcinogenesis of hepatic carcinoma, and it may provide new evidence for therapeutic application in hepatic carcinoma.


Assuntos
Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt , Animais , Carcinoma Hepatocelular/diagnóstico , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas Experimentais/diagnóstico , Neoplasias Hepáticas Experimentais/metabolismo , Camundongos , Camundongos Nus , RNA Longo não Codificante/genética
19.
Aquat Toxicol ; 215: 105289, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491707

RESUMO

Mifepristone (RU486), a clinical abortion agent and potential endocrine disruptor, binds to progestin and glucocorticoid receptors and has multiple functional importance in reproductive physiology. A long-term exposure of RU486 resulted in masculinization of female fish, however, the epigenetic landscape remains elusive. Recent studies demonstrated that long non-coding RNAs (lncRNAs) might play potential roles in epigenetic modulation of sex differentiation, ovarian cancer and germline stem cell survival. To further understand the influence of RU486 exposure on epigenetic regulation, we performed a comparative investigation on sex-biased gonadal lncRNAs profiles using control XX/XY and RU486-induced sex reversed XX Nile tilapia (Oreochromis niloticus) by RNA-seq. In total, 962 sexually differentially expressed lncRNAs and their target genes were screened from the gonads of control and sex reversed fish. In comparison with the control XX group, sex reversal induced by RU486 treatment led to significant up-regulation of 757 lncRNAs and down-regulation of 221 lncRNAs. Hierarchical clustering analysis revealed that global lncRNA expression profiles in RU486-treated XX group clustered into the same branch with the control XY, whereas XX control group formed a separate branch. The KEGG pathway enrichment analysis showed that the cis-target genes between RU486-XX and control-XX were concentrated in NOD - like receptor signaling pathway, Cell adhesion molecules (CAMs) and Biosynthesis of amino acids. Real-time PCR and in situ hybridization experiments demonstrate that lncRNAs showing intense fluctuation during RU486 treatment are also sexually dimorphic during early sex differentiation, which further proves the intimate relationship between lncRNAs and sex differentiation and sexual transdifferentiation. Taken together, our data strongly indicates that a long-term exposure of RU486 resulted in sex reversal of XX female fish and the altered expression of sexually dimorphic lncRNAs might partially account for the sex reversal via epigenetic modification.


Assuntos
Ciclídeos/genética , Ciclídeos/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Gônadas/metabolismo , Mifepristona/toxicidade , Progestinas/antagonistas & inibidores , RNA Longo não Codificante/genética , Caracteres Sexuais , Animais , Feminino , Genoma , Gônadas/efeitos dos fármacos , Masculino , Fases de Leitura Aberta/genética , Ovário/efeitos dos fármacos , Ovário/metabolismo , RNA Longo não Codificante/metabolismo , Reprodutibilidade dos Testes , Testículo/efeitos dos fármacos , Testículo/metabolismo , Fatores de Tempo , Distribuição Tecidual/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
20.
Zhonghua Yi Xue Za Zhi ; 99(35): 2761-2767, 2019 Sep 17.
Artigo em Chinês | MEDLINE | ID: mdl-31550799

RESUMO

Objective: To investigate the mechanisms of lncRNA on the occurrence and development of NOA by constructing ceRNA regulation network of lncRNA, miRNA and mRNA. Methods: Samples of adult human testis were obtained from NOA patients and OA patients with normal spermatogenesis (controls), recruited from the Reproductive Medicine Center of Nanfang Hospital from June 2017 to June 2018. Differentially expressed lncRNAs and mRNAs in testicular tissues from patients with NOA were identified by microarray analysis in previous association study. In this study, differentially expressed lncRNAs and mRNA were used to construct the ceRNA regulatory network in NOA and clarify the interaction relationship among lncRNA, miRNA and mRNA. GeneMANIA database was used to construct Protein-Protein Interaction (PPI) of the mRNAs in ceRNA regulatory network. WebGestalt toolkit was employed to perform gene function and pathway enrichment analyses of those coding genes. Finally, qRT-PCR and dual luciferase reporter system were employed for further experimental validation. Results: The ceRNA regulatory network of lncRNA, miRNA and mRNA consists of 21 nodes and 26 edges, of which 4 lncRNAs, 13 miRNAs and 4 mRNAs. 19 proteins were found to interact with the mRNA coding proteins in ceRNA regulatory network by PPI analysis. Gene oncology and KEGG pathway enrichment analyses indicate these coding genes were significantly enriched in pentose metabolic process and pentose phosphate pathway. Furthermore, lncRNA ANXA2P3 was found binding with miR-613 and miR-206 to inhibit mRNA TKT expression. Conclusion: lncRNAs exert an important role in the occurrence and development of NOA via ceRNA regulatory network, which could be used as new biomarkers for NOA treatment.


Assuntos
Azoospermia/genética , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , Humanos , Masculino , MicroRNAs/genética , RNA Mensageiro/genética
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