RESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as novel players in cancer metabolism. lncRNA small nucleolar RNA host gene 7 (SNHG7) plays an oncogenic role in prostate cancer (PCa). However, the role and mechanism of SNHG7 in PCa metabolism remain largely undefined. METHODS: A cohort of 30 PCa tumors and their counterparts were collected. qRT-PCR was employed to detect target gene expression and RNA stability. CCK-8 assay was used to assess cell viability. N6-methyladenosine (m6A) level was measured by a commercial kit. Cell glycolysis was evaluated by measuring glucose uptake, lactate, ATP production and Extracellular acidification rate (ECAR). Bioinformatics analysis and RNA immunoprecipitation (RIP) assay were used to verify the interactions among SNHG7, serine/arginine-rich splicing factor 1 (SRSF1) and c-Myc. RESULTS: SNHG7 and c-Myc were highly expressed in PCa tissues and cells. Methyltransferase-like 3 (METTL3)-mediated m6A modification of SNHG7 and enhanced its stability. Silencing of SNHG7 suppressed proliferation and glycolysis in PCa cells. Mechanistically, SNHG7 regulated c-Myc via interacting with SRSF1. Gain- and loss-of function experiments revealed that SNHG7 promoted glycolysis via SRSF1/c-Myc axis in PC-3 and DU-145 cells. CONCLUSION: METTL3-stabilized lncRNA SNHG7 accelerates glycolysis in PCa via SRSF1/c-Myc axis and inspires the understanding of m6A roles in lncRNA metabolism and tumor progression.
Assuntos
MicroRNAs , Neoplasias da Próstata , RNA Longo não Codificante , Carcinogênese/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Glicólise/genética , Humanos , Masculino , Metiltransferases/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismoRESUMO
Diabetic retinopathy is one of the microvascular complications in diabetic patients and the leading cause of blindness worldwide. The levels of METTL3, lncRNA SNHG7, KHSRP, MKL1, endothelial and mesenchymal markers were determined by RT-qPCR or western blot assays in vitro and in vivo. H&E staining was used to observe the retinal structure in a mouse model of DR. The expression levels of METTL3 and SNHG7 were significantly downregulated in DR patients, DR mice and high glucose-induced HRMECs cells. Notably, METTL3 installed the m6A modification and enhanced the stability of SNHG7. Besides, METTL3 inhibited HRMECs EndoMT by promoting the expression of SNHG7. Additionally, SNHG7 was found to weaken MKL1 mRNA stability by binding to the RNA-binding protein KHSRP. Furthermore, we verified that METTL3 regulated EndoMT in DR through the SNHG7/MKL1 axis. We conclude that METTL3 regulates endothelial-mesenchymal transition in DR via the SNHG7/KHSRP/MKL1 axis, providing a new target for DR treatment.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , RNA Longo não Codificante , Camundongos , Animais , Transferases , Retinopatia Diabética/genética , RNA Longo não Codificante/genética , Metiltransferases/genéticaRESUMO
BACKGROUND: New evidence from clinical and fundamental researches suggests that SNHG7 is involved in the occurrence and development of carcinomas. And the increased levels of SNHG7 are associated with poor prognosis in various kinds of tumors. However, the small sample size was the limitation for the prognostic value of SNHG7 in clinical application. The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of SNHG7 in various cancers. METHODS: Articles related to the SNHG7 as a prognostic biomarker for cancer patients, were comprehensive searched in several electronic databases. The enrolled articles were qualified via the preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology checklists. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was further used to validate our results. RESULTS: We analyzed 2418 cancer patients that met the specified criteria. The present research indicated that an elevated SNHG7 expression level was significantly associated with unfavorable overall survival (OS) (HR = 2.45, 95% CI: 2.12-2.85, p <0.001). Subgroup analysis showed that high expression levels of SNHG7 were also significantly associated with unfavorable OS in digestive system cancer (HR = 2.31, 95% CI: 1.90-2.80, p <0.001) and non-digestive system cancer (HR = 2.67, 95% CI: 2.12-3.37, p <0.001). Additionally, increased SNHG7 expression was found to be associated with tumor stage and progression (III/IV vs. I/II: HR = 1.76, 95% CI: 1.57-1.98, p <0.001). Furthermore, elevated SNHG7 expression significantly predicted lymph node metastasis (LNM) (HR = 1.98, 95% CI: 1.74-2.26, p <0.001) and distant metastasis (DM) (HR = 2.49, 95% CI: 1.88-3.30, p <0.001) respectively. No significant heterogeneity was observed among these studies. SNHG7 was significantly upregulated in four cancers and the elevated expression of SNHG7 predicted shorter OS in four cancers, worse DFS in five malignancies and worse PFI in five carcinomas based on the validation using the GEPIA on-line analysis tool. CONCLUSIONS: The present analysis suggests that elevated SNHG7 is significantly associated with unfavorable OS, tumor progression, LNM and DM in various carcinomas, and may be served as a promising biomarker to guide therapy for cancer patients.
Assuntos
Carcinoma/genética , Carcinoma/mortalidade , Neoplasias/genética , Neoplasias/mortalidade , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Biologia Computacional , Humanos , Metástase Linfática/genética , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
Hepatocellular carcinoma (HCC) is a malignant tumor with high mortality and severe complication in China. Numerous studies have shown that long noncoding RNAs (lncRNAs) are involved in the regulation of various processes in cancer cells. Our research aimed to investigate the underlying mechanism of the lncRNA small nucleolar RNA host gene 7 (SNHG7) in HCC development. The expression of SNHG7, microRNA-122-5p (miR-122-5p), and Forkhead box K2 (FOXK2) was assessed via quantitative real-time polymerase chain reaction. 3-(4,5) -dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and transwell assays were performed to measure cell viability, migration, and invasion, respectively. The relative protein levels were detected by Western blot. The relationships between miR-122-5p and SNHG7 or FOXK2 were predicted by online software and then confirmed by dual-luciferase reporter assay. Animal experiments were conducted to clarify the effects of SNHG7 on proliferation in vivo. To begin with, SNHG7 was upregulated, while miR-122-5p was downregulated in HCC tissues and cells. Downregulation of SNHG7 inhibited cell growth and metastasis. Interestingly, SNHG7 could abolish the effects of miR-122-5p on HCC cells. Furthermore, miR-122-5p targeted FOXK2 and miR-122-5p recovered the effects of FOXK2 downregulation on cell growth and metastasis in HCC cells. Besides, SNHG7 facilitated HCC tumor growth in vivo through the miR-122-5p/FOXK2 axis. The lncRNA SNHG7 boosted the development of HCC by regulating FOXK2 through sponging miR-122-5p.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Long non-coding RNA (lncRNA) is of great significance in diagnosing and prognosis of human diseases. This study aims to explore the expression of lncRNA SNHG7 in infants with neonatal sepsis and further evaluate the diagnostic and prognostic value of SNHG7 in neonatal sepsis. The expression levels of serum SNHG7 in 81 neonates were detected by quantitative real-time-PCR (qRT-PCR). The correlations between SNHG7 and clinicopathological indicators were estimated by the Pearson correlation coefficient. The receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of SNHG7. Kaplan-Meier survival curve and multivariate Cox regression analysis were conducted to evaluate the prognostic value of SNHG7 in neonatal sepsis. The expression level of serum SNHG7 was significantly upregulated in the neonatal sepsis group compared to the controls, and overexpressed SNHG7 showed clinical diagnostic value for neonatal sepsis. It was observed that the SNHG7 levels were positively correlated with some indicators representing the degree of inflammation. Follow-up analysis and multivariate Cox regression revealed that the death probability of neonates with high SNHG7 level was higher than that with low SNHG7 levels, and SNHG7 was an independent factor of poor prognosis in neonates with neonatal sepsis. Together, our findings show that highly expressed SNHG7 has the potential to be a diagnostic biomarker for neonates with neonatal sepsis and was closely related to the poor prognosis of neonatal sepsis.
Assuntos
Sepse Neonatal , RNA Longo não Codificante , Sepse , Recém-Nascido , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sepse Neonatal/diagnóstico , Sepse Neonatal/genética , Prognóstico , Biomarcadores , Curva ROC , Sepse/diagnóstico , Sepse/genéticaRESUMO
Accumulated evidence has manifested that long noncoding RNA (lncRNA) is involved in the progress of Parkinson's disease (PD). SNHG7, a novel lncRNA, has been found to be involved in tumorigenesis. However, SNHG7 expression and its functional effects on PD remain uncharted. Rotenone (Rot) was adopted to construct PD models in Sprague-Dawley (SD) rats and SH-SY5Y cells, respectively. The expression levels of caspase 3, tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba1) in SD rat striatum were measured via immunohistochemistry and western blot. Additionally, the expressions of inflammatory cytokines (interleukin 1ß [IL-1ß], IL-6, tumor necrosis factor α) and oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase) in the brain tissues were examined using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Moreover, the protein levels of tumor necrosis factor receptor-associated factor (TRAF5), I-κB, nuclear factor-κB (NF-κB), HO-1, Nrf2 were detected via western blot. Bioinformatics was applied to predict the targeting relationship between SNHG7, miR-425-5p, and TRAF5. Dual-luciferase activity assay and RNA immunoprecipitation assays were conducted to verify their interactions. In comparison to healthy donors, SNHG7 was found upregulated while miR-425-5p expression was downregulated in PD patients. Functional experiments confirmed that SNHG7 downregulation or miR-425-5p overexpression attenuated neuronal apoptosis in the Rot-mediated PD model, TH-positive cell loss, and microglial activation by mitigating inflammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR-425-5p and promoted TRAF5 mediated inflammation and oxidative stress. Inhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR-425-5p/TRAF5/NF-κB signaling pathway modulated inflammation and oxidative stress, and similar results were observed in the Rot-mediated rat model of PD.
Assuntos
Apoptose/genética , Regulação para Baixo/genética , MicroRNAs/sangue , NF-kappa B/metabolismo , Doença de Parkinson/sangue , RNA Longo não Codificante/sangue , Transdução de Sinais/genética , Fator 5 Associado a Receptor de TNF/metabolismo , Animais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Inflamação/genética , Inflamação/metabolismo , Masculino , MicroRNAs/genética , Neurônios/metabolismo , Estresse Oxidativo/genética , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-Dawley , TransfecçãoRESUMO
Long non-coding RNA small nucleolar RNA host gene 7 (SNHG7) was reported to regulate the pathogenesis of ischemic stroke. The study aimed to disclose SNHG7 role in oxygen and glucose deprivation (OGD)-induced Neuro-2a (N2a) cell disorders. An OGD injury cell model was established using N2a cells. The expression of SNHG7, microRNA-134-5p (miR-134-5p) and fibroblast growth factor 9 (FGF9) was determined by quantitative real-time polymerase chain reaction. Protein expression was detected by western blot. Cell viability and Lactate Dehydrogenase (LDH) leakage were determined by cell counting kit-8 and LDH activity detection assays. Oxidative stress was investigated by Superoxide Dismutase and Catalase activity assays as well as Malondialdehyde and Reactive Oxygen Species detection kits. Cell apoptosis and caspase-3 activity were severally demonstrated by flow cytometry and caspase-3 activity assays. The interaction between miR-134-5p and SNHG7 or FGF9 was predicted by online databases, and identified by mechanism assays. OGD treatment decreased SNHG7 and FGF9 expression, but increased miR-134-5p expression. OGD treatment repressed cell viability, promoted LDH leakage and induced oxidative stress and apoptosis in N2a cells, which was rescued by SNHG7 overexpression. SNHG7 acted as a sponge for miR-134-5p, and regulated OGD-triggered cell damage by associating with miR-134-5p. Additionally, miR-134-5p depletion protected N2a cells from OGD-induced injury by targeting FGF9. Ectopic SNHG7 expression protected against OGD-induced neuronal cell injury by inducing FGF9 through sponging miR-134-5p, providing a novel therapeutic target for ischemic stroke.
Assuntos
MicroRNAs , RNA Longo não Codificante , Fator 9 de Crescimento de Fibroblastos/metabolismo , Glucose/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neurônios/metabolismo , Oxigênio/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
OBJECTIVE: To determine the role of quercetin in non-small cell lung carcinoma (NSCLC) and the biological outcomes using transfection experiments. MATERIALS AND METHODS: Real-time reverse transcription-PCR and data collection were performed to determine lncRNA and miRNA levels. Transwell assay was performed to assess the invasion ability of cells. Apoptosis of cells digested with trypsin was determined using the Annexin V-FITC kit. Luciferase activity was determined using the luciferase reporter gene system. Cell viability was tested using the Cell Counting Kit-8 assay. A xenograft mouse model was established to investigate the effects of quercetin on tumor growth. RESULTS: The expression levels of the long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) were elevated in NSCLC cells, and the expression levels of the microRNA miR-34a-5p were decreased compared with those in normal cells. Further investigation revealed that quercetin decreased SNHG7 and elevated miR-34a-5p levels in NSCLC cells (p < .05). The luciferase reporter gene assay, RNA-binding protein immunoprecipitation assay, and transfection experiments revealed target-binding sequences between SNHG7 and miR-34a-5p. Overexpression of SNHG7 or miR-34a-5p inhibitor promoted NSCLC cell proliferation and accelerated tumor cell growth and metastasis. The therapeutic effect of quercetin on NSCLC cells was counteracted by co-transfection of SNHG7 mimic or miR-34a-5p inhibitor. Quercetin inhibited the survival, proliferation, migration, and invasion of NSCLC cells and enhanced their apoptosis. Using the mouse model, quercetin was shown to inhibit tumor growth. CONCLUSIONS: Quercetin inhibits the proliferation and induces apoptosis of NSCLC cells by mediating signaling via the lncRNA SNHG7/miR-34a-5p pathway.
Assuntos
Antioxidantes/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/biossíntese , Quercetina/farmacologia , RNA Longo não Codificante/biossíntese , Células A549 , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Quercetina/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
PURPOSE: Glioma has been categorized as the most common primary malignant brain tumor. Long non-coding RNA SNHG7 (lncRNA SNHG7) has been recognized in various cancers as a possible oncogene. In this study, the effect of SNHG7 on glioma cells was investigated. MATERIALS AND METHODS: Thirty glioma tissues and adjacent normal tissues were collected. Pc-SNHG7, sh-SNHG7, miR-342-3p mimic and miR-342-3p inhibitor were transfected into the glioma cells. Cell Counting Kit-8, Transwell and scratch assay evaluated glioma cells viability, invasion and migration, respectively. TargetScan, Starbase and dual-luciferase reporter were used to predict and confirm the target genes and potential binding sites of SNHG7, miR-342-3p and AKT2. Relative miR-342-3p and AKT2 expressions were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pearson's analysis was adopted for correlation analysis between SNHG7, miR-342-3p and AKT2. RESULTS: SNHG7 expressions in glioma tissues and cells were increased, upregulation of SNHG7 promotes cell viability, invasion and migration. SNHG7 was shown to bind with miR-342-3p, and upregulating SNHG7 reduced miR-342-3p expression. AKT2 was the target gene of miR-342-3p, and miR-342-3p expression was decreased while AKT2 expression was increased in glioma tissues. High expression of miR-342-3p inhibited cell viability, invasion and migration and reduced AKT2 expression, whereas low expression of miR-342-3p did the opposite effect. CONCLUSIONS: Upregulating SNHG7 might promote glioma cells viability, migration and invasion with the regulation of decreasing miR-342-3p level and increasing AKT2 level.
Assuntos
Glioma/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Glioma/patologia , Humanos , Invasividade Neoplásica/fisiopatologia , Regulação para CimaRESUMO
Dentin-pulp regeneration requires dental pulp stem cells (DPSCs), but the role of long noncoding RNAs (lncRNAs) during this process remains unclear. Here, we cultured human DPSCs in osteogenic/odontogenic medium for 14 days and analyzed cells via RNA-sequencing. The data were validated by quantitative reverse transcription-polymerase chain reaction and lncRNA-microRNA (miRNA)-messenger RNA (mRNA) networks were constructed to reveal the potential competing endogenous RNA regulatory role of lncRNAs. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis were performed. One lncRNA, SNHG7, was identified and validated by genetic shRNA silencing. A total of 89 lncRNAs, 1,636 mRNAs, and 113 miRNAs were differentially expressed after differentiation. Bioinformatics identified an array of affected signaling pathways including phosphoinositide-3-kinase-protein kinase B, transforming growth factor-ß, and Wnt. mRNAs were enriched in cell migration, cell differentiation, stem cell development, ossification, and skeletal development. One lncRNA, SNHG7, was indentified to inhibit the odonto/osteogenic differentiation of DPSCs when silenced. In summary, we reveal several lncRNAs that significantly change during DPSC differentiation, including SNHG7. This reveals new targets for dentin-pulp complex regeneration and tissue engineering.
Assuntos
Polpa Dentária/crescimento & desenvolvimento , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genética , Diferenciação Celular/genética , Biologia Computacional , Polpa Dentária/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , RNA Mensageiro/genética , Células-Tronco/metabolismoRESUMO
Emerging evidence suggests that microRNA plays a pivotal role in cell proliferation. Our previous research has certified that miR-146a attenuates osteoarthritis through the regulation of cartilage homeostasis. However, little information about the function of miR-146a in bone marrow-derived mesenchymal stem cells (BMSCs) proliferation and the underlying mechanism was available. Therefore, this study aims at investigating the role of miR-146a on the proliferation of BMSCs and the possible mechanisms involved. The function of miR-146a on BMSCs proliferation was studied through overexpression and knockdown of miR-146a or the indicated long noncoding RNAs (lncRNAs) in BMSCs and then the proliferation rate of the BMSCs were detected by Cell Counting Kit-8 assay, colony formation assay. Besides, flow cytometry was used to test the cell cycle state of BMSCs modified by overexpression or knockdown of miR-146a or lncRNA EPB41L4A-AS1 (EPB41L4A Antisense RNA 1) and small nucleolar RNA host gene 7 (SNHG7). The expression level of marker genes involved in modulating cell proliferation was evaluated by quantitative polymerase chain reaction and western blot analysis. We discovered that the knockdown of miR-146a significantly promoted BMSCs proliferation. Moreover, miR-146a could bind to and inhibit endogenous expression of EPB41L4A-AS1 and SNHG7. Further study demonstrated that overexpression of EPB41L4A-AS1 and SNHG7 significantly enhanced proliferation of BMSCs. For the first time, we certified that miR-146a suppressed BMSCs proliferation, but EPB41L4A-AS1 and SNHG7 promoted BMSCs proliferation in the present study. Mechanistically, miR-146a significantly inhibited BMSCs proliferation partly through miR-146a/EPB41L4A-AS1 SNHG7/cell proliferation signaling pathway axis.
Assuntos
Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , RNA Longo não Codificante/genética , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Células-Tronco Mesenquimais/citologia , Transdução de Sinais/genéticaRESUMO
Thyroid cancer (TC) has been characterized as the most common malignant malady of the endocrine system. Small nucleolar RNA host gene 7 (SNHG7) has been reported to serve as a key regulator in a large number of human cancer types, but its role in TC and the underlying regulatory mechanism have never been evaluated yet. The present study indicated that the expression of SNHG7 was markedly higher in TC cell lines. Knockdown of SNHG7 led to a suppression of TC cell progression and migration. Acyl-CoA synthetase long-chain family member 1 (ACSL1) has also been demonstrated as an oncogene in many cancers. Herein an inhibition of ACSL1 after SNHG7 knockdown was captured. Further, the suppressing effects of SNHG7 knockdown on TC cell processes were counteracted by ACSL1 overexpression. Data from online bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays validated the interaction between microRNA-449a (miR-449a) and SNHG7 or ACSL1. It was also verified that SNHG7 sequestered miR-449a and therefore elevated ACSL1 expression levels. To conclude, the current study indicated that SNHG7 promoted proliferation and migration of TC cells by sponging miR-449a and therefore upregulating ACSL1. The present study may provide more explorations about the molecular regulation mechanism of long noncoding RNAs in TC progression.
Assuntos
Coenzima A Ligases/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Neoplasias da Glândula Tireoide/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Coenzima A Ligases/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/genética , Oncogenes , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/patologia , Transfecção , Regulação para Cima/genéticaRESUMO
BACKGROUND: Nasopharyngeal carcinoma (NPC), with distinct geographical distribution, has gathered public attention. Despite that radiotherapy and chemotherapy are applied to treat NPC, cell metastasis still cannot be avoided. Numerous works have elucidated that lncRNAs are essential players in the development of multiple cancers. LncRNA SNHG7 has been reported as a contributing factor in the occurrence of certain cancers, but its mechanism in NPC deserves further investigation. The purpose of the study is to figure out the role and molecular regulation mechanism of SNHG7 in NPC. METHODS: The role of SNHG7 in NPC was verified by CCK-8, colony formation, EdU staining, western blot and capase-3 assays. The interactions between SNHG7/ELAVL1 and miR-514a-5p were confirmed by RNA pull down, RT-qPCR, RIP and luciferase reporter assays. RESULTS: SNHG7 was upregulated in NPC cells, and absence of SNHG7 suppressed cell proliferation as well as promoted cell apoptosis in NPC. Furthermore, SNHG7 was confirmed to bind with miR-514a-5p and negatively modulate miR-514a-5p expression. Besides, miR-514a-5p was found to be able to bind with ELAVL1 and negatively regulate ELAVL1 mRNA and protein expressions. In the end, rescue assays demonstrated that the miR-514a-5p deficiency restored the NPC progression inhibited by SNHG7 silence, and ELAVL1 partly counteracted the restoration caused by miR-514a-5p inhibitor in HNE1 cells. CONCLUSIONS: LncRNA SNHG7 promotes the proliferation and migration of nasopharyngeal carcinoma by miR-514a-5p/ ELAVL1 axis.
Assuntos
Proteína Semelhante a ELAV 1/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteína Semelhante a ELAV 1/genética , Humanos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Regulação para CimaRESUMO
BACKGROUND: Osteoarthritis (OA) is one of the most common rheumatic diseases of which clinical symptoms includes swelling, synovitis and inflammatory pain, affect patients' daily life. It was reported that non-coding RNAs play vital roles in OA. However, the regulation mechanism of ncRNA in OA pathogenesis has not been fully elucidated. METHODS: The expression of SNHG7, miR-34a-5p and SYVN1 was detected using qRT-PCR in tissues, serum and cells. The protein expression of SYVN1, PCNA, cleavage-caspase 3, beclin1 and LC3 were measured using western blot. The RNA immunoprecipitation (RIP), RNA pulldown, and luciferase reporter assays were used to verify the relationship between SNHG7, miR-34a-5p and SYVN1. The MTT and flow cytometry assay was performed to detected cell proliferation and cell apoptosis respectively. RESULTS: In this study, SNHG7 and SYVN1 expression were down-regulated, but miR-34a-5p was up-regulated in OA tissues and IL-1ß treated cells compared with normal tissues and chondrocyte. Functional investigation revealed that up-regulated SNHG7 or down-regulated miR-34a-5p could promote cell proliferation and inhibit cell apoptosis and autophagy in OA cells. More than that, RIP, pulldown and luciferase reporter assay was applied to determine that miR-34a-5p was a target miRNA of SNHG7 and SYVN1 was a target mRNA of miR-34-5p. Rescue experiments showed that overexpression of miR-34a reversed high expression of SNHG7-mediated suppression of apoptosis and autophagy as well as promotion of proliferation, while its knockdown inhibited cell apoptosis and autophagy and promoted cell proliferation which could be impaired by silencing SYVN1. In addition, SNHG7 regulated SYVN1 through sponging miR-34a-5p. CONCLUSION: SNHG7 sponged miR-34a-5p to affect cell proliferation, apoptosis and autophagy through targeting SYVN1 which provides a novel sight into the pathogenesis of OA.
Assuntos
Apoptose/fisiologia , Autofagia/fisiologia , MicroRNAs/metabolismo , Osteoartrite/metabolismo , RNA Longo não Codificante/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Apoptose/genética , Autofagia/genética , Western Blotting , Proliferação de Células , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Humanos , MicroRNAs/genética , Osteoartrite/genética , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real , Ubiquitina-Proteína Ligases/genética , Regulação para CimaRESUMO
Long noncoding RNAs (lncRNAs) are reported to be involved in the pathology of numerous cancers, including neuroblastoma (NB). lncRNA SNHG7 has been recognized as a carcinogen in several cancers, but its role in NB progression remains unknown. Our study revealed that SNHG7 expression was markedly higher in NB tissues than that in nontumor tissues. Besides, upregulated SNHG7 was greatly correlated with poor overall survival of NB patients. Functionally, the loss-of-function assays demonstrated that knockdown of SNHG7 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition in NB cells. Mechanically, the bioinformatics analysis predicted that miR-653-5p was the shared partner of SNHG7 and signal transducer and activator of transcription 2 (STAT2). Unsurprisingly, we further confirmed that SNHG7 could interact with miR-653-5p and therefore functioned as the ceRNA of STAT2 so as to regulate STAT2 expression in NB cells. Moreover, STAT2 expression was in inverse proportion to miR-653-5p level but in positive proportion to SNHG7 level in NB tissues. Importantly, the repressed NB progression induced by silenced SNHG7 was reversed by STAT2 overexpression or miR-653-5p inhibitors. Jointly, our findings elucidated SNHG7 facilitated NB progression through the miR-653-5p/STAT2 pathway, providing a novel therapeutic target and prognostic biomarker for this disease.
Assuntos
MicroRNAs/genética , Neuroblastoma/genética , Neuroblastoma/metabolismo , RNA Longo não Codificante/genética , Fator de Transcrição STAT2/metabolismo , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Pré-Escolar , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Retroalimentação Fisiológica , Feminino , Técnicas de Silenciamento de Genes , Humanos , Lactente , Masculino , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Neuroblastoma/patologia , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , Regulação para CimaRESUMO
Diabetic retinopathy (DR) is the serious complication of type 2 diabetes mellitus, which could lead to visual impairment. Growing evidence have revealed the involvement of long non-coding RNAs (lncRNAs) in the pathogenesis of DR. Thus, this study was performed to investigate the role of lncRNA SNHG7 (small nucleolar RNA host gene 7) in high glucose (HG)-induced proliferation, migration, and angiogenesis of human retinal endothelial cells (hRECs). We discovered that SNHG7 was decreased in hRECs under HG stimuli. Although SNHG7 had no influence on cell viability, migration and angiogenesis under condition, overexpression of SNHG7 inhibited the HG-induced cell proliferation, migration and angiogenesis, as well as vascular endothelial growth factor (VEGF) expression in HG condition. In terms of mechanism, we found that SNHG7 directly inhibited miR-543, which targeted the 3'-UTR of Silent information regulator T1 (SIRT1) mRNA and subsequently downregulated the VEGF expression in hRECs. Ultimately, upregulation of miR-543 or inhibition of SIRT1 both abrogated the effect of SNHG7 on HG-induced angiogenesis. Collectively, our results suggested that SNHG7 is a potential molecular target for attenuating HG-induced angiogenesis in the DR through regulation of the miR-543-mediated SIRT1/VEGF pathway.
Assuntos
Retinopatia Diabética/metabolismo , Células Endoteliais/efeitos dos fármacos , Glucose/farmacologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Retina/citologia , Neovascularização Retiniana/prevenção & controle , Sirtuína 1/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Regulação para Baixo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Glucose/metabolismo , Humanos , Retina/efeitos dos fármacos , Neovascularização Retiniana/induzido quimicamente , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
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/genéticaRESUMO
The long non-coding RNA SNHG7 (small nucleolar RNA host gene 7) has been reported to be involved in various cancers as a potential oncogene. However, the functions and molecular mechanisms of SNHG7 in glioblastoma (GBM) are largely unknown. In the present study, we showed that the expression of SNHG7 was significantly upregulated in GBM tissues and cell lines compared with non-cancerous brain tissues. Furthermore, we found that SNHG7 knockdown remarkably suppressed the proliferation, migration and invasion of A172 and U87â¯cells while inducing their apoptosis. Subsequently, we showed that SNHG7 knockdown significantly inhibited tumor growth and metastasis in vivo by using xenograft experiments in nude mice. In terms of mechanism, we found that SNHG7 directly inhibited miR-5095, which targeted the 3' UTR of CTNNB1 mRNA and subsequently downregulated the Wnt/ß-catenin signaling pathway in GBM. Using rescue experiments, we demonstrated that SNHG7 promoted the proliferation, migration and invasion of GBM cells through the inhibition of miR-5095 and concomitant activation of Wnt/ß-catenin signaling pathway. Taken together, the SNHG7/miR-5095 axis might be a potential target for the development of effective GBM therapy.
Assuntos
Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Apoptose , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Glioblastoma/patologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
BACKGROUND: Acute coronary syndrome (ACS) is one of the common causes of cardiovascular death. The related lncRNAs were novel approaches for early diagnosis and intervention. This paper focused on the clinical function of SNHG7 for patients after PCI. METHODS: The expression of SNHG7 was assessed in ACS patients. The predictive roles of SNHG7 were unveiled by the ROC curve. The relationship between SNHG7 and Gensini scores was judged by Pearson analysis. One-year follow-up was conducted and all patients were catalogued into different groups based on the prognosis. The qRT-PCR, K-M curve, and Cox regression analysis were performed to document the prognostic significance of SNHG7. RESULTS: SNHG7 was highly expressed in ACS and its three subtypes. SNHG7 showed a certain value in predicting ACS, UA, NSTEMI, and STEMI. Gensini is a closely correlated indicator of SNHG7. The declined expression of SNHG7 was observed in the non-MACE and survival groups. The risk of MACE and death was increased in the group with high expression of SNHG7. SNHG7 was an independent biomarker in patients with ACS after PCI. CONCLUSIONS: SNHG7 might be a diagnostic and prognostic tool for ACS patients.
Assuntos
Síndrome Coronariana Aguda , Biomarcadores , Intervenção Coronária Percutânea , RNA Longo não Codificante , Humanos , Síndrome Coronariana Aguda/cirurgia , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/diagnóstico , RNA Longo não Codificante/genética , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Prognóstico , Idoso , Valor Preditivo dos Testes , Curva ROCRESUMO
As a representative item of chemical carcinogen, MNNG is closely associated with the onset of gastric cancer (GC), where N6-methyladonosine (m6A) RNA methylation is recognized as a critical epigenetic event. In our previous study, we found that the m6A modification by methyltransferase METTL3 was up-regulated in MNNG-exposed malignant GES-1 cells (MC cells) compared to control cells in vitro, and long non-coding RNA SNHG7 as a downstream target of the METTL3. However, the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC remains unclear. In the present study, we continuously investigate the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC. RIP-PCR and m6A-IP-qPCR were used to examine the molecular mechanism underlying the METTL3/m6A/SNHG7 axis in MNNG-induced GC. A METTL3 knockout mice model was constructed and exposed by MNNG. Western blot analysis, IHC analysis, and RT-qPCR were used to measure the expression of METTL3, SNHG7, and EMT markers. In this study, we demonstrated that in MNNG-induced GC tumorigenesis, the m6A modification regulator METTL3 facilitates cellular EMT and biological functions through the m6A/SNHG7 axis using in vitro and in vivo models. In conclusion, our study provides novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.