Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 852
Filtrar
1.
Genet Test Mol Biomarkers ; 25(1): 31-41, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33372851

RESUMO

Objective: The long-chain noncoding RNA (lncRNA) TINCR has been associated with the development and progression of bladder cancer. In this study, we analyzed the correlation between lncRNA TINCR single-nucleotide polymorphisms (SNPs) and bladder cancer susceptibility risk. Methods: The genotypes of the lncRNA TINCR rs2288947 and rs8113645 loci in 125 surgically treated bladder cancer patients and 125 controls were analyzed by Sanger sequencing. A dual-luciferase reporter gene assay was used to detect the binding of the microRNAs miR-1247-3p and miR-30c-2-3p with the lncRNA TINCR. The receiver operating characteristic curve was used to analyze the value of expression levels of the lncRNA TINCR and the microRNAs miR-1247-3p and miR-30c-2-3p in the diagnosis of bladder cancer. Results: The bladder cancer susceptibility risk of the rs2288947 G allele carriers was 2.32 times higher compared with the A allele carriers (95% confidence interval [CI]: 1.58-3.42, p < 0.01); The bladder cancer susceptibility risk of the rs8113645 T allele carriers was 0.33 times compared with the C allele carriers (95% CI: 0.19-0.55, p < 0.01). lncRNA TINCR was more highly expressed in bladder cancer tissues than controls (p < 0.01). The lncRNA TINCR rs2288947 A>G variation was associated with increased expression of lncRNA TINCR in bladder cancer tissues, and the rs8113645 C > T was associated with decreased expression. The expression levels of the lncRNA TINCR in cancer and paracancerous tissues showed a significant negative correlation with that of miR-1247-3p and miR-30c-2-3p (r = -0.89, -0.78, -0.81, and -0.66, all p < 0.01). The dual-luciferase reporter gene assay results indicate that the lncRNA TINCR rs2288947 G allele is the target of miR-1247-3p, and the rs8113645 C allele is the target of miR-30c-2-3p. Conclusion: The lncRNA TINCR rs2288947 A>G is associated with increased bladder cancer risk and rs8113645 C > T is associated with decreased susceptibility. These two SNP loci are associated with lncRNA TINCR expression levels; however, further studies are needed for validation.


Assuntos
Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , RNA Neoplásico , Neoplasias da Bexiga Urinária , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
2.
Medicine (Baltimore) ; 99(51): e23525, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371075

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) can predict the prognosis of patients with coronary heart disease (CHD) after obtaining percutaneous coronary intervention (PCI), while this conclusion still needs to be further confirmed. Therefore, this study attempted to explore the relationship between lncRNA and prognosis in CHD patients after PCI. METHODS: The database was retrieved from China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, and EMBASE. Hazard ratios (HRs) and its 95% confidence interval (CIs) were applied to assess the prognostic effects of lncRNA on overall survival (OS). RevMan 5.3 and STATA 16.0 software were used to perform meta-analysis. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This review provided a comprehensive overview of the relationship between lncRNA and prognosis in CHD patients after PCI, and offered recommendations for clinical practices or guidelines.


Assuntos
Doença das Coronárias/cirurgia , Intervenção Coronária Percutânea/estatística & dados numéricos , RNA Longo não Codificante/biossíntese , Humanos , Prognóstico , Projetos de Pesquisa
3.
Medicine (Baltimore) ; 99(28): e21059, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664121

RESUMO

LncRNA plasmacytoma variant translocation 1 (PVT1) has been recognized as an oncogenic lncRNA, which participates in the migration and invasion of many kinds of cancer cells and the development of cancers. In the present study, we explored its clinical significance and prognostic value in muscle invasive bladder cancer (MIBC).A total of 98 MIBC patients' samples were collected, who had undergone radical cystectomy from the March 2013 to December 2018. The associations between PVT1 expression and clinical data were calculated using the Chi-test. Overall survival curves were determined by the Kaplan-Meier technique and contrasted via log-rank test. We utilized univariate and multivariate Cox proportional hazard models to examine the HR and 95% CI.The expression levels of PVT1 were significantly higher in MIBC tissues than that in normal bladder tissues (P < .001). PVT1 expression was significantly correlated with tumor grade (P = .009), margin (P = .002), T stage (P = .02), and lymph node metastasis (P < .001). MIBC patients with high PVT1 expression level had shorter overall survival than those with low PVT1 expression level (log-rank test, P = .004). Multivariate Cox regression analysis showed that PVT1 expression level (HR = 2.381, 95% CI: 1.821-7.012, P = .014) was an independent factor in predicting the overall survival of MIBC patients.In summary, increased PVT1 expression in MIBC patients is correlated with a higher MIBC stage and is significantly associated with poor prognosis for MIBC patients, which may provide new insights into new therapeutic strategy and postoperative intervention against bladder cancer.


Assuntos
RNA Longo não Codificante/biossíntese , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Biomarcadores Tumorais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Regulação para Cima
4.
Anticancer Res ; 40(6): 3097-3108, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487604

RESUMO

BACKGROUND/AIM: C-C motif chemokine ligand 18 (CCL18) is overexpressed in the microenvironment of tumors, promotes invasion and metastasis and is thus important for the therapeutic outcome of many tumor entities. The Gs-coupled seven-transmembrane receptor GPR30 is known as both a CCL18 and an estrogen receptor; its activation by estradiol leads to a transactivation of membrane-tethered pro-heparin-binding EGF-like growth factor and the MAPK/ERK pathway. We examined whether this signaling pathway remains the same under CCL18 stimulation, as opposed to estradiol stimulation. MATERIALS AND METHODS: We investigated the effects of CCL18 on the lung cancer cell line A549, that show low GPR30 expression and the breast cancer cell lines MCF-7, that has high GPR30 expression and MDA-MB-231. These cells were stimulated in different media with CCL18 and then analyzed by qPCR, In-Cell Western®, western blot and ELISA. RESULTS: Many similarities on the effect of CCL18 on the already known estradiol-activated signaling pathway via the G protein-coupled estrogen receptor GPR30 were identified. GPR30 is involved in the expression of matrix metalloproteinases (MMPs), which may play a role in the transactivation of ERK-1/-2 via the cleavage of membrane-bound HB-EGF, via Src-related tyrosine kinases and Gßγ-subunits. With increasing CCL18 concentration, the expression of MMP7 decreased in A549 cells. With decreasing estrogen content of the medium, there was an increasing effect of CCL18 on the inhibition of the relative expression of MMP7. Inhibition of GPR30 with G15 also resulted in a decrease in the relative expression of MMP7, irrespective of the subsequent stimulation with CCL18. This is a rather unexpected result, because the estrogen estradiol and CCL18 both activate GPR30. MCF-7 cells which express more GPR30 did not show any dependence of the relative MMP7 expression on CCL18 except in estrogen-free FCS medium. CCL18 induced an increased relative ERK activation in In-Cell western (ICW) at A549 cells. Stimulation with CCL18 caused decreased ERK activation with simultaneous inhibition of adenylate cyclase in MCF-7. However, stimulation with CCL18 and simultaneous inhibition of cyclooxygenase in MCF-7 resulted in increased ERK activation. In A549, stimulation with CCL18 and co-incubation with dbcAMP resulted in decreased ERK activation in both ICW and Western blot. CONCLUSION: In summary, the Gs-coupled receptor GPR30 plays an important role in the signaling pathway of CCL18. CCL18 and estradiol may not lead to the same signaling pathway after activating GPR30.


Assuntos
Quimiocinas CC/metabolismo , Estradiol/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Células A549 , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Quimiocinas CC/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Células MCF-7 , Metaloproteinase 7 da Matriz/biossíntese , Metaloproteinase 7 da Matriz/genética , Fosforilação , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Receptores Estrogênicos/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Transdução de Sinais
5.
Am J Physiol Cell Physiol ; 319(1): C105-C115, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32374674

RESUMO

Transforming growth factor-ß (TGF-ß)-induced fibroblast activation is a key pathological event during tissue fibrosis. Long noncoding RNA (lncRNA) is a class of versatile gene regulators participating in various cellular and molecular processes. However, the function of lncRNA in fibroblast activation is still poorly understood. In this study, we identified growth arrest-specific transcript 5 (GAS5) as a novel regulator for TGF-ß-induced fibroblast activation. GAS5 expression was downregulated in cultured fibroblasts by TGF-ß and in resident fibroblasts from bleomycin-treated skin tissues. Overexpression of GAS5 suppressed TGF-ß-induced fibroblast to myofibroblast differentiation. Mechanistically, GAS5 directly bound mothers against decapentaplegic homolog 3 (Smad3) and promoted Smad3 binding to Protein phosphatase 1A (PPM1A), a Smad3 dephosphatase, and thus accelerated Smad3 dephosphorylation in TGF-ß-treated fibroblasts. In addition, GAS5 inhibited fibroblast proliferation. Importantly, local delivery of GAS5 via adenoviral vector suppressed bleomycin-induced skin fibrosis in mice. Collectively, our data revealed that GAS5 suppresses fibroblast activation and fibrogenesis through inhibiting TGF-ß/Smad3 signaling, which provides a rationale for an lncRNA-based therapy to treat fibrotic diseases.


Assuntos
Fibroblastos/metabolismo , RNA Longo não Codificante/biossíntese , Transdução de Sinais/fisiologia , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/metabolismo , Animais , Fibroblastos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , RNA Longo não Codificante/genética , Dermatopatias/genética , Dermatopatias/patologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo
6.
Life Sci ; 254: 117778, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407850

RESUMO

Long non-coding RNA (LncRNA) involved in types of physiological insults and diseases via regulating the responses of complex molecular, including cerebral ischemia-reperfusion (I/R) injury. LncRNA SNHG16 played a potential role in ketamine-induced neurotoxicity. In this study, we utilized an in vitro cell model of I/R to examine the specific function and mechanism of LncRNA SNHG16 in oxygen-glucose deprivation and reperfusion (OGD/R) induced SH-SY5Y cells. After in vitro treatment of OGD/R, the lower the SH-SY5Y cell survival, the higher cell the apoptosis and increased caspase-3 activity was observed. Also, OGD/R induced endoplasmic reticulum stress (ERS) through increasing GRP78 and CHOP expressions and down-regulated LncRNA SNHG16 in SH-SY5Y cells. Conversely, LncRNA SNHG16 overexpression promoted OGD/R induced SH-SY5Y cell survival, suppressed its apoptosis, and caspase-3 activity. GRP78 and CHOP expressions were significantly suppressed in LncRNA SNHG16 overexpressing cells. MiR-106b-5p expression was increased and LIMK1 expression was down-regulated in OGD/R induced SH-SY5Y cells, and these effects were reversed by LncRNA SNHG16 overexpression, respectively. Moreover, LIMK1 is a direct target of MiR-106b-5p, and knockdown of LIMK1 reversed the effects of LncRNA SNHG16 on OGD/R-induced SH-SY5Y cells biology. Altogether, these results confirmed an important neuroprotection role of LncRNA SNHG16 in OGD/R induced SH-SY5Y cells injury, and miR-106b-5p/LIMK1 signal axis was involved in the action of LncRNA SNHG16.


Assuntos
Sobrevivência Celular/fisiologia , Quinases Lim/fisiologia , MicroRNAs/fisiologia , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/fisiologia , Traumatismo por Reperfusão/metabolismo , Apoptose/fisiologia , Caspase 3/metabolismo , Células Cultivadas , Regulação para Baixo , Estresse do Retículo Endoplasmático , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico/biossíntese , Humanos , Quinases Lim/genética , Quinases Lim/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais/fisiologia , Fator de Transcrição CHOP/biossíntese
8.
Medicine (Baltimore) ; 99(13): e19606, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221083

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary epithelial tumor with poor prognosis. There are increasing evidences that long non-coding RNAs (lncRNAs) are dysregulated in multifarious tumors, revealing potential significant role of lncRNAs in tumorigenesis.We used the ICC dataset retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus database to obtain the lncRNAs expression profiles and identify potential prognostic lncRNAs for predicting the prognosis in ICC. Univariate and multivariate Cox regression analyses were performed to construct a prognostic index (PI). Furthermore, coexpression analysis and functional assessment were performed to initially investigate the function of these prognostic lncRNAs.A total of 255 differentially expressed lncRNAs (DElncRNAs) were identified among two RNA sequencing dataset of a total 63 ICC patients with 98 samples using R platform. Thirteen of 255 DElncRNAs were identified as prognostic lncRNAs and used for a PI. Patients with high PI were associated with poor prognostic (P = .0064), and the Cox regression showed consistent result (P = .042). The time-dependent receiver operating characteristic analysis showed the PI performed well in ICC survival prediction with an area under curve of 0.921, 0.801, and 0.717 for 1-, 3-, and 5-year survival, respectively.In conclusion, we included 13 identified prognostic DElncRNAs and constructed a prognostic signature/PI. ICC patient with higher PI was associated with poorer prognosis. However, the clinical role as well as biological functions of constructed PI and these prognostic DElncRNAs need to be verified in future study.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC
9.
Int J Biochem Cell Biol ; 122: 105742, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32173520

RESUMO

The role of microRNAs (miRNAs) in chronic kidney disease (CKD) is relatively well established, but much less is known about the role(s) of long noncoding RNAs (lncRNAs). Transforming growth factor ß1 (TGF-ß1) mediates inflammatory and fibrogenic signaling in CKD via the transcription factor Smad3; however, the extent of lncRNAs-based regulation of TGF-ß1 signaling in CKD remains unknown. Herein, we identified np_4334, a lncRNA we named Ptprd-IR, whose promoter contains a highly-conserved site for Smad3 binding. Smad3 knockout (KO) eliminated Ptprd-IR upregulation in a murine model of obstructive nephropathy. Furthermore, Ptprd-IR KO in renal tubular epithelial cell cultures blocked TGF-ß1- and interleukin-1ß (IL-1ß)-mediated NF-κB inflammatory signaling but did not impact TGF-ß1-triggered Smad3 pathway activity and fibrosis. Accordingly, Ptprd-IR overexpression (OE) upregulated TGF-ß1- and IL-1ß-mediated NF-κB pathway activation and production of pro-inflammatory cytokines but did not influence TGF-ß1-mediated fibrogenic signaling. Additionally, transfection of obstructed kidneys with Ptprd-IR-directed shRNA attenuated the inflammatory response via NF-κB but did not impact TGF-ß1/Smad3-mediated fibrogenesis. Overall, our findings demonstrate that the lncRNA Ptprd-IR stimulates the inflammatory response in kidneys and advocate Ptprd-IR as a possible therapeutic target for CKD.


Assuntos
Nefrite/genética , Nefrite/metabolismo , RNA Longo não Codificante/genética , Fator de Crescimento Transformador beta1/metabolismo , Animais , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Interleucina-1beta/metabolismo , Íntrons , Camundongos , NF-kappa B/metabolismo , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Proteína Smad3/metabolismo , Transfecção , Regulação para Cima
10.
Int J Biochem Cell Biol ; 122: 105740, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32173521

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in regulation of gene expression and are involved in pathogenesis of different diseases including cancer. Recent studies suggested the lncRNA Colon cancer associated transcript-1 (CCAT1) to act as putative oncogene. In this study, to elucidate the role of this lncRNA in endometrial cancer, we examined its expression in normal endometrium and type 1 endometrial cancer and knocked down its expression in endometrial cancer cell lines followed by transcriptome and pathway analyses. METHODS: CCAT1 expression was examined in 100 tissue samples of normal endometrium and type 1 endometrial cancer tissues by means of RT-qPCR. Knockdown of CCAT1 expression in HEC-1B and RL95/2 endometrial cancer cells was performed by siRNA transfection. Affymetrix GeneChip arrays were used to elucidate the effect of both lncRNAs on the transcriptome of these cell lines. RESULTS: Median CCAT1 expression was found to be 9.3-fold higher in endometrial cancer when compared to normal endometrium (p < 0.05). In contrast to premenopausal endometrium and G1, G2 and G3 graded endometrial cancer, CCAT1 expression was nearly absent in postmenopausal tissue. Knockdown of CCAT1 by transient siRNA transfection significantly reduced proliferation of HEC-1B cancer cells in vitro by 35.5 % 6 days after transfection and notably reduced their colony formation ability. Affymetrix microarray and Ingenuity pathway analyses revealed a set of up- or down-regulated genes in transfected ERα-negative HEC-1B cells forming a network controlled by the key regulators TNF and TP53, including genes known to be involved in growth control, providing putative molecular mechanisms underlying the observed growth inhibition of HEC-1B cells. In contrast, CCAT1 knockdown in ERα-positive RL95/2 cells did not significantly affect proliferation, but resulted in down-regulation of a network of ERα target genes. CONCLUSIONS: Given that the lncRNA CCAT1 was found to be overexpressed in endometrial cancer, affected the growth of HEC-1B cells and the expression of growth regulatory genes, our data suggest CCAT1 to exert oncogenic functions in endometrial cancer and encourage further studies to examine to what extent this lncRNA might be a potential therapy target in this cancer entity.


Assuntos
Adenocarcinoma/genética , Neoplasias do Endométrio/genética , RNA Longo não Codificante/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Técnicas de Silenciamento de Genes , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante/biossíntese , Transcriptoma
11.
Int J Mol Med ; 45(4): 1150-1162, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124940

RESUMO

Our previous study demonstrated that intranasal administration of histone deacetylase inhibitor sodium butyrate (NaB) exhibits therapeutic effects on a mouse model of allergic rhinitis (AR). However, whether NaB is effective on AR when administered orally and prophylactically, as well as its potential effects on gene expression, remained unknown. The present study aimed to investigate the preventive effect of NaB on AR when added to the diet of newly weaned mice and to evaluate the changes in long non­coding (lnc)RNA and mRNA expression profiles in the nasal mucosa. Mice were randomly divided into three groups as follows: i) Control (C) group, (no treatment); ii) AR group [treated with ovalbumin (OVA)]; and iii) NaB + AR group (treated with OVA and NaB). The NaB + AR group was administered NaB in their feed (30 g/kg chow), whereas the other two groups were fed normal feed between 3 and 6 weeks of age. At 7 weeks of age, OVA administration was initiated to induce AR in the AR and NaB + AR groups. Following model establishment, behavioral assessments, western blotting and gene expression analysis were performed. NaB exhibited a preventive effect in the murine AR model, diminished the increases in histone deacetylase 1 (HDAC1) and HDAC8 expression and increased OVA­induced acetylation of histone H3 at lysine 9. In addition, NaB increased the AR­associated low expression of interleukin 2 (IL­2), interferon Î³ and IL­17 and decreased the expression of IL­4, IL­5 and transforming growth factor ß1. Gene Ontology and pathway analyses revealed the top 10 pathways among the groups. Octamer­binding transcription factor 1, ecotropic viral integration site 1 and paired box 4 were predicted to be target genes of lncRNA (NONMMUT057309). Thus, NaB may exhibit a preventive effect on AR. Additionally, the lncRNA and mRNA expression profiles in the nasal mucosa of mice with AR differed significantly following NaB treatment. These results may provide insights into the pathogenesis of AR and suggest new treatment targets.


Assuntos
Ácido Butírico/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Mucosa Nasal/metabolismo , RNA Longo não Codificante/biossíntese , RNA Mensageiro/biossíntese , Rinite Alérgica/prevenção & controle , Animais , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/patologia , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/metabolismo
12.
Int J Mol Med ; 45(4): 1250-1260, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124944

RESUMO

The problems caused by diabetes mellitus (DM) and its related complications are gaining increasing attention. In our previous study, the abnormal proliferation of small intestinal epithelial cells (IECs) were observed in diabetic mice. However, little is known regarding the potential underlying mechanism. In the present study, the abnormal proliferation of IECs in DM and the marked upregulation of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was observed. Additionally, knockdown of MALAT1 significantly reduced abnormal IESC proliferation in DM mice. Bioinformatics analysis and luciferase reporter assays revealed that microRNA (miR)­129­5p was directly targeted by MALAT1. Moreover, the results of the bioinformatics prediction and luciferase assays demonstrated that MALAT1 directly interacted with SRY­box 9 (SOX9). Furthermore, MALAT1 silencing was observed to attenuate the abnormal proliferation of IESCs through the SOX9­mediated WNT/ß­catenin signaling pathway. Knockdown of MALAT1 downregulated SOX9 expression by binding to miR­129­5p, thereby inhibiting the abnormal proliferation of IESCs via the WNT/ß­catenin signaling pathway.


Assuntos
Proliferação de Células , Diabetes Mellitus Experimental/metabolismo , Regulação para Baixo , Células Epiteliais/metabolismo , Intestino Delgado/metabolismo , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , Animais , Diabetes Mellitus Experimental/patologia , Células Epiteliais/patologia , Intestino Delgado/patologia , Masculino , Camundongos
13.
J Orthop Surg Res ; 15(1): 38, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013985

RESUMO

BACKGROUND: Osteosarcoma (OS) is the most common type of primary bone tumor that mainly affects adolescents and young adults. The present study explored the role of lncRNA GAS8-AS1 in OS. METHODS: A total of 48 OS patients were selected from the 82 OS patients admitted by Luoyang Orthopedic Hospital of Henan Province between May 2010 and May 2013. Transient cell transfections, Transwell cell migration and invasion assay, RT-qPCR, and patient follow-up were carried out during the research. RESULTS: The results showed that GAS8-AS1 was downregulated, while UCA1 was upregulate in cancer tissues in comparison to adjacent non-cancer tissues of OS patients. GAS8-AS1 was not affected by clinical stage. Follow-up study showed that downregulated GAS8-AS1 in cancer tissues was closely correlated with poor survival. GAS8-AS1 and UCA1 were inversely correlated in cancer tissues. Overexpression of UCA1 failed to affect the expression of GAS8-AS1, while overexpression of GAS8-AS1 led to downregulated expression of UCA1 in OS cells, while the molecular mediators between these two lncRNAs are unknown. Overexpression of GAS8-AS1 did not affect OS cell proliferation but significantly inhibited cancer cell migration and invasion. Overexpression of UCA1 promoted the migration and invasion of OS cells and attenuated the effects of overexpressing GAS8-AS1. CONCLUSIONS: Therefore, GAS8-AS1 may inhibit OS cell migration and invasion by downregulating oncogenic UCA1.


Assuntos
Neoplasias Ósseas/metabolismo , Movimento Celular/fisiologia , Regulação para Baixo/fisiologia , Osteossarcoma/metabolismo , RNA Longo não Codificante/biossíntese , Adolescente , Adulto , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/biossíntese , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Criança , Feminino , Seguimentos , Humanos , Masculino , Invasividade Neoplásica/patologia , Osteossarcoma/patologia , RNA Longo não Codificante/antagonistas & inibidores , Adulto Jovem
14.
Exp Eye Res ; 193: 107960, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32035086

RESUMO

Homo sapiens MIR7-3 host gene (MIR7-3HG), a long non-coding RNA, has been reported to be connected with the progression of several tumors and could be served as a prognostic marker. Our study intends to explore the biological function and potential molecular mechanism of MIR7-3HG in Retinoblastoma (Rb) progression. Two Rb cell lines Y79 and WERI-Rb-1 were applied to perform functional assays. Expression of MIR7-3HG in Rb tissues and cells were determined with the support of GEO database and qRT-PCR experiment. The effects of MIR7-3HG on cell activity and apoptosis were assessed through cell counting kit 8 and flow cytometry assays, respectively. Targeted connections between MIR7-3HG and miR-27a-3p, as well as miR-27a-3p and PEG10 were speculated by bioinformatics prediction software and verified by performing dual luciferase assays. Further interrelationships among MIR7-3HG, miR-27a-3p, and PEG10 were explored through rescue assays. MIR7-3HG overexpression was detected in Rb tissues and cell lines. Depletion of MIR7-3HG reduced the activity of Rb cells and increased the apoptosis of Rb cells, and vice versa. In addition, further exploration perceived that MIR7-3HG, miR-27a-3p, and PEG10 generated a competing endogenous RNA (ceRNA) mechanism to regulate Rb cells activity and apoptosis. Our results indicated that MIR7-3HG functioned as a ceRNA to up-regulate PEG10 expression via sponging miR-27a-3p to promote the proliferation of Rb cells and suppress the apoptosis of Rb cells, exhibiting a group of potential target molecules for Rb treatment in the future.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Células Ganglionares da Retina/patologia , Neoplasias da Retina/genética , Retinoblastoma/genética , Apoptose , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Humanos , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , RNA Neoplásico/metabolismo , Células Ganglionares da Retina/metabolismo , Neoplasias da Retina/metabolismo , Neoplasias da Retina/patologia , Retinoblastoma/metabolismo , Retinoblastoma/patologia
15.
Int J Mol Sci ; 21(4)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098245

RESUMO

Many studies have revealed that circulating long noncoding RNAs (lncRNAs) regulate gene and protein expression in the process of hepatic fibrosis. Liver fibrosis is a reversible wound healing response followed by excessive extracellular matrix accumulation. In the development of liver fibrosis, some lncRNAs regulate diverse cellular processes by acting as competing endogenous RNAs (ceRNAs) and binding proteins. Previous investigations demonstrated that overexpression of lncRNAs such as H19, maternally expressed gene 3 (MEG3), growth arrest-specific transcript 5 (GAS5), Gm5091, NR_002155.1, and HIF 1alpha-antisense RNA 1 (HIF1A-AS1) can inhibit the progression of liver fibrosis. Furthermore, the upregulation of several lncRNAs [e.g., nuclear paraspeckle assembly transcript 1 (NEAT1), hox transcript antisense RNA (Hotair), and liver-enriched fibrosis-associated lncRNA1 (lnc-LFAR1)] has been reported to promote liver fibrosis. This review will focus on the functions and mechanisms of lncRNAs, the lncRNA transcriptome profile of liver fibrosis, and the main lncRNAs involved in the signalling pathways that regulate hepatic fibrosis. This review provides insight into the screening of therapeutic and diagnostic markers of liver fibrosis.


Assuntos
Regulação da Expressão Gênica , Cirrose Hepática/metabolismo , Fígado/metabolismo , RNA Longo não Codificante/biossíntese , Transdução de Sinais , Transcriptoma , Animais , Biomarcadores/metabolismo , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia
16.
Cancer Biother Radiopharm ; 35(2): 109-119, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32077748

RESUMO

Background: Long noncoding RNAs could serve as a candidate target for prostate cancer (PCa) diagnosis and treatment. The current study aimed to investigate the role and functions of SNHG1 in PCa cells. Materials and Methods: Abnormal expression of SNHG1, survival analysis, and target gene were determined or predicted by bioinformatics techniques. Gene expressions at transcriptional and translational levels were determined by Quantitative Real-time PCR and Western blotting, respectively. Cell viability, growth, and apoptosis rate were detected by Cell Counting Kit-8, colony formation assay and flow cytometry. Results: The results showed that SNHG1 was highly expressed in PCa tissues, which was accompanied by decreased miR-377-3p expression and poor overall survival rate, and that miR-377-3p was predicted as the target of SNHG1 in PCa cells. Moreover, SNHG1 counteracted the effects of miR-377-3p on inhibiting cell growth and promoting apoptosis of PCa cells. Furthermore, miR-377-3p counteracted the effects of AKT2 on promoting cell viability, growth, and suppressing apoptosis of PCa cells. In addition, AKT2 expression was proved to be regulated by miR-377-3p. Conclusions: The SNHG1/miR-377-3p/AKT2 regulatory axis in PCa cells was disclosed. The upregulated AKT2 might be a result of dysregulated interaction balance between the expressions of miR-377-3p and SNHG1. Based on such discoveries, the intervention of SNHG1/miR-377-3p/AKT2 axis could be further explored in the treatment of PCa.


Assuntos
MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/biossíntese
17.
Int J Biol Markers ; 35(1): 47-56, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31960744

RESUMO

OBJECTIVE: To evaluate the function of long non-coding RNA ANRIL (CDKN2B-AS1) in laryngeal squamous cell cancer (LSCC), and to explore the underlying mechanism. METHODS: The expression levels of CDKN2B-AS1 in LSCC tissues and cell lines (Tu177, HN4, AMC-HN-8 and NP69) were determined by reverse transcription quantitative PCR (RT-qPCR). AMC-HN-8 cells were then transfected with siRNAs of CDKN2B-AS1. The effects of CDKN2B-AS1 on cell proliferation, cell cycle, and apoptotic protein were determined by CCK-8 assay, flow cytometry analysis, and western blot, respectively. Dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the targets of CDKN2B-AS1. The miR-324-5p mimics or miR-324-5p inhibitor and ROCK1 over-expression plasmids were also transfected into AMC-HN-8 cells for further analysis. RESULTS: CDKN2B-AS1 was upregulated in LSCC tissues, and the upregulation of CDKN2B-AS1 was correlated with overall survival, advanced clinical stage, and lymph node metastasis. In AMC-HN-8 cells, the knockdown of CDKN2B-AS1 by siRNA inhibited cell viability, blocked cell cycle in G1 phase, and increased the expression levels of cyclin-dependent kinase inhibitor 1A (p21), cleaved caspase3, and cleaved PPoly (ADP-Ribose) polymerase 1. Results of dual luciferase reporter assay showed that miR-324-5p could bind to CDKN2B-AS1 or Rho-associated coiled-coil containing protein kinase 1 (ROCK1). Finally, over-expression of ROCK1 in AMC-HN-8 cells revised the inhibitory effect of CDKN2B-AS1 siRNA on cell growth. DISCUSSION: The upregulation of CDKN2B-AS1 was correlated with overall survival, advanced clinical stage, and lymph node metastasis and promoted LSCC cell growth via miR-324-5p/ROCK1 axis.


Assuntos
Neoplasias Laríngeas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Quinases Associadas a rho/metabolismo , Sequência de Bases , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ciclo Celular/fisiologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , MicroRNAs/biossíntese , MicroRNAs/genética , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Regulação para Cima , Quinases Associadas a rho/genética
18.
Artif Cells Nanomed Biotechnol ; 48(1): 393-407, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31913710

RESUMO

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


Assuntos
Apoptose , Regulação Leucêmica da Expressão Gênica , Genes Supressores de Tumor , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Neoplasias do Colo do Útero/metabolismo , Feminino , Células HeLa , Humanos , MicroRNAs , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
19.
J Biochem Mol Toxicol ; 34(3): e22435, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31916649

RESUMO

The long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been reported to sustain the proliferation of acute myeloid leukemia (AML) cells through downregulating cell cycle regulators p27kip1 . Yet, the foundational mechanism of UCA1 in AML pathologies remains unclear. Herein, we found an escalation of UCA1 expression and suppression of miR-204 expression in pediatric AML patients and cells. UCA1 silencing suppressed cell proliferative abilities, promoted apoptotic rates, decreased Ki67, and increased cleaved caspase-3 in AML cells. Moreover, UCA1 sponged miR-204 and suppressed its expression. UCA1 overexpression inversed the miR-204 suppressed proliferation and promoted apoptosis. UCA1 also boosted the expression of SIRT1, a miR-204 target, via the sponging interaction. Furthermore, miR-204 inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression, while UCA1 overexpression inversed the inhibitory effects in AML cells. Our findings concluded that UCA1 downregulation repressed cell proliferation and promoted apoptosis through inactivating SIRT1 signals by upregulating miR-204 in pediatric AML.


Assuntos
Apoptose , Proliferação de Células , Inativação Gênica , Leucemia Mieloide Aguda , MicroRNAs , Proteínas de Neoplasias , RNA Longo não Codificante , RNA Neoplásico , Sirtuína 1 , Linhagem Celular Tumoral , Criança , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo
20.
Cancer Biother Radiopharm ; 35(1): 72-76, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31910343

RESUMO

Background: MAGI2-AS3 has been reported to be a tumor suppressor in breast cancer and bladder cancer. This study analyzed the role of MAGI2-AS3 in non-small cell lung cancer (NSCLC). Results: The authors found that MAGI2-AS3 and suppressor of cytokine signaling 1 (SOCS-1) were both downregulated in NSCLC. MAGI2-AS3 and SOCS-1 were significantly and positively correlated in NSCLC tumor tissues. During follow-up, low levels of MAGI2-AS3 and SOCS-1 were found to be significantly correlated with patients' poor survival. In NSCLC cells, MAGI2-AS3 overexpression mediated the upregulated, while miR-155 expression mediated the downregulated SOCS-1 overexpression. RNA binding analysis showed that MAGI2-AS3 may be a sponge of miR-155. Cell proliferation revealed decreased cell proliferation rate of NSCLC cells after MAGI2-AS3 and SOCS-1 overexpression. MiR-155 played an opposite role and reduced the effects of MAGI2-AS3 overexpression. Conclusion: Therefore, MAGI2-AS3 upregulates cytokine signaling 1 by sponging miR-155 to inhibit NSCLC cell proliferation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Guanilato Quinases/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/fisiologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina/genética , Regulação para Cima
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA