Small Nucleolar RNA Host Gene 1 Expression Research Articles

Dysregulation of lncRNA SNHG1/miR-145 axis affects the biological function of human carotid artery smooth muscle cells as a mechanism of carotid artery restenosis.

Carotid angioplasty and stenting have developed into reliable options for patients with carotid stenosis. However, postoperative restenosis remains a serious and unresolved problem. Restenosis is partly caused by the proliferation of vascular smooth muscle cells. As certain long non-coding RNAs (lncRNAs) affect cell proliferation and migration, the present study aimed to investigate them as novel biomarkers for restenosis development and to further reveal the potential underlying mechanisms. The expression of lncRNA small nucleolar RNA host gene 1 (SNHG1) and microRNA145 (miR-145) in human carotid artery smooth muscle cells (hHCtASMCs) was analyzed using reverse transcription-quantitative PCR. In addition, a luciferase reporter assay was performed to investigate the interaction between SNHG1 and miR-145. The effects of the SNHG1/miR-145 axis on the proliferation and migration of hHCtASMCs were evaluated by Cell Counting Kit-8 and Transwell assays. Serum SNHG1 and miR-145 expression levels were increased and decreased, respectively, in patients with restenosis (all P<0.001). High SNHG1 and low miR-145 were identified as risk factors for restenosis onset (all P<0.01). Furthermore, decreasing SNHG1 expression levels in hHCtASMCs inhibited cell proliferation and migration. The luciferase reporter assay and expression results demonstrated that miR-145 may be a target of SNHG1 and mediated the effects of SNHG1 on hHCtASMC proliferation and migration. The results obtained suggested that abnormal expression of SNHG1 and miR-145 may be risk factors for restenosis. The present study revealed that the SNHG1/miR-145 axis regulates hHCtASMC proliferation and migration, indicating its potential for restenosis prevention and treatment.

Long Noncoding RNA SNHG14 Promotes Ischemic Brain Injury via Regulating miR-199b/AQP4 Axis.

Ischemic stroke is the leading cause of disability worldwide. Long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of cerebral ischemia. This study aimed to investigate the role and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in ischemic brain injury. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in mice. The expression of SNHG14 in MCAO mouse model was detected by quantitative real-time PCR (qRT-PCR). The levels of SNHG14, microRNA-199b (miR-199b) and aquaporin 4 (AQP4) in oxygen-glucose deprivation (OGD)-stimulated BV2 cells were determined by qRT-PCR or western blot assay. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The levels of pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The levels of oxidative stress markers were examined using commercial kits. The relationships among SNHG14, miR-199b and AQP4 were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. SNHG14 was up-regulated in MCAO mouse model. Depletion of SNHG14 lessened cerebral ischemia in MCAO mouse model. SNHG14 silencing inhibited inflammation and oxidative stress in OGD-exposed BV2 cells. MiR-199b level was decreased, while AQP4 level was increased in OGD-treated BV2 cells. Knockdown of miR-199b reversed the effect of SNHG14 knockdown on ischemic damage in OGD-stimulated BV2 cells. Moreover, AQP4 overexpression abolished the effect of miR-199b on ischemic injury in OGD-treated BV2 cells. Furthermore, SNHG14 indirectly regulate AQP4 expression by sponging miR-199b. Knockdown of SNHG14 attenuated ischemic brain injury by inhibiting inflammation and oxidative stress through the miR-199b/AQP4 axis.

LncRNA SNHG5 promotes cervical cancer progression by regulating the miR-132/SOX4 pathway

Background The long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) has been verified as a crucial regulator in many types of tumours but not clear in cervical cancer (CC). This study aims to investigate the effect and further mechanisms of lncRNA SNHG5 in CC. Methods The expression of SNHG5 and miR-132, as well as SOX4 (sex-determining region Y-box 4) mRNA expression were determined by quantitative real-time PCR (qRT-PCR). The protein level of SOX4 and epithelial-mesenchymal transition (EMT)-related proteins were evaluated by western blot. Then, Edu and Transwell assay were performed to assess the proliferation, migration and invasion of CC cells. RNA immunoprecipitation (RIP) and RNA pull-down assay were conducted to explore the relationship between SNHG5 and miR-132. Results SNHG5 and SOX4 were upregulated, and miR-132 was downregulated in CC tissues and cell lines. SNHG5 was positively correlated with FIGO stage (p = .003) and lymph node metastasis (p = .001). Pearson’s correlation analysis conveyed that SNHG5 was positively correlated with SOX4, and miR-132 was negatively correlated with SOX4 and SNHG5. Knockdown of SNHG5 in vitro reduced CC cell proliferation, migration and invasion through regulating miR-132. Moreover, overexpression of miR-132 restrained CC cell proliferation, migration, and invasion through targeting SOX4, and SNHG5 enhanced SOX4 expression via negatively regulating miR-132. Conclusion SNHG5 promotes SOX4 expression to accelerate CC cell proliferation, migration and invasion through negatively regulating miR-132.

Upregulation of long non-coding RNA SNHG16 promotes diabetes-related RMEC dysfunction via activating NF-κB and PI3K/AKT pathways

Diabetic retinopathy (DR) is a severe diabetes-induced eye disease, in which its pathological phenomena basically include abnormal proliferation, migration, and angiogenesis of microvascular endothelial cells in the retina. Long non-coding RNAs (lncRNAs) have been proven to be important regulators in various biological processes, but their participation in DR remains largely undiscovered. In the present study, we aimed to unveil the role of lncRNA small nucleolar RNA host gene 16 (SNHG16) in regulating the functions of human retinal microvascular endothelial cells (hRMECs) under a high-glucose (HG) condition. We found that SNHG16 expression was significantly upregulated in hRMECs treated with HG. Functionally, SNHG16 could facilitate hRMEC proliferation, migration, and angiogenesis. Moreover, SNHG16 was associated with nuclear factor κB (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. Mechanistically, SNHG16 could promote hRMEC dysfunction by sequestering microRNA (miR)-146a-5p and miR-7-5p to act as a competing endogenous RNA (ceRNA) with interleukin-1 receptor-associated kinase 1 (IRAK1) and insulin receptor substrate 1 (IRS1). In conclusion, our results illustrated the potential role of SNHG16 in facilitating hRMEC dysfunction under HG treatment, providing a novel approach for DR therapy.

SNHG1 knockdown upregulates miR-376a and downregulates FOXK1/Snail axis to prevent tumor growth and metastasis in HCC

Long non-coding RNAs (lncRNAs), microRNAs (miRNAs or miRs), and genes are emerging players in cancer progression. In the present study, we explored the roles and interactions of oncogenic lncRNA small nucleolar RNA host gene 1 (SNHG1), miR-376, forkhead box protein K1 (FOXK1), and Snail in hepatocellular carcinoma (HCC). Expression of SNHG1, miR-376, and FOXK1 in HCC was characterized in clinical HCC tissues of 75 patients with HCC. The interactions between SNHG1 and miR-376 and between miR-376 and FOXK1 were predicted and confirmed by dual-luciferase reporter gene and RNA immunoprecipitation assays. Overexpression and knockdown experiments were performed in HCC cells to examine the effects of the SNHG1/miR-376/FOXK1/Snail axis on viability, apoptosis, invasiveness, and migrating abilities. Their effects on tumor growth and metastasis were validated in nude mouse models. SNHG1 and FOXK1 were upregulated, and miR-376a was downregulated in HCC. SNHG1 knockdown contributed to suppression of HCC cell viability, invasion, and migration properties and promotion of apoptosis. SNHG1 could competitively bind to miR-376a to upregulate its target gene FOXK1, which upregulated Snail. SNHG1 knockdown delayed cancer progression both in vitro and in vivo by upregulating miR-376a and downregulating FOXK1 and Snail. SNHG1 knockdown exerts anti-tumor activity in HCC, suggesting a therapeutic target.

LncRNA SNHG15 Knockdown Protects Against OGD/R-Induced Neuron Injury by Downregulating TP53INP1 Expression via Binding to miR-455-3p.

Cerebral ischemia-reperfusion (I/R) injury is the common symptom of ischemic stroke, which poses a heavy burden to human health. Long non-coding RNA (lncRNA) is indicated to be a critical regulator in cerebral ischemia. This study aims to reveal the effects of lncRNA small nucleolar RNA host gene 15 (SNHG15) on oxygen-glucose deprivation and reoxygenation (OGD/R)-induced neuron injury and underlying mechanism. The expression levels of SNHG15, microRNA-455-3p (miR-455-3p) and tumour protein p53 inducible nuclear protein 1 (TP53INP1) mRNA were determined by quantitative real time polymerase chain reaction in P12 cells. The protein levels of TP53INP1, cleaved caspase-3, caspase-3, B-cell lymphoma-2 and BCL2-associated x protein (Bax) were detected by western blot in P12 cells. Cell viability and apoptosis were revealed by cell counting kit-8 assay and flow cytometry analysis, respectively, in P12 cells. Caspase-3 activity, the levels of tumor necrosis factor-α and interleukin-1β and the production of reactive oxygen species (ROS) were severally determined by caspase-3 activity assay, Enzyme-linked immunosorbent assay and ROS detection assay in P12 cells. The binding relationship between miR-455-3p and SNHG15 or TP53INP1 was predicted by starbase online database, and identified by dual-luciferase reporter, RNA pull-down or RNA immunoprecipitation assay. SNHG15 expression and the mRNA and protein levels of TP53INP1 were dramatically upregulated, while miR-455-3p expression was apparently downregulated in OGD/R-induced PC12 cells. SNHG15 silencing hindered the effects of OGD/R treatment on cell viability, apoptosis, inflammation and oxidative in PC12 cells; however, these impacts were restored after miR-455-3p inhibitor transfection. Additionally, SNHG15 acted as a sponge of miR-455-3p and miR-455-3p bound to TP53INP1. SNHG15 contributed to OGD/R-induced neuron injury by regulating miR-455-3p/TP53INP1 axis, which provided a novel insight to study lncRNA-directed therapy in ischemia stoke.

Influence of pentoxifylline on gene expression of PAG1/ miR-1206/ SNHG14 in ischemic heart disease

The regulation by immune checkpoint is able to prevent excessive tissue damage caused by ischemia reperfusion (I/R); therefore, the study aims to investigate the behavior of phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) mRNA, miR-1206 and small nucleolar RNA host gene 14 (SNHG14) during I/R and intake of pentoxifylline (PTX) as a protective drug. The relative expression level of PAG1/miR-1206/SNHG14 was determined by qRT-PCR. Cardiac tissue levels of cytotoxic T-lymphocyte associated antigen 4 (CTLA4) and PAG1 protein expression were determined by ELISA technique. The regulatory T cells achieved by the flow cytometry. The results found that the relative expression of SNHG14 was significantly upregulated in I/R, but suppressed in PTX treated groups with enhancement of the relative expression level of miR-1206. The gene and protein expression of PAG1 were downregulated with effective doses of PTX. The results showed that (30 and 40 mg/kg bwt) PTX dose suppressed the CTLA4 development significantly. The mean of the regulatory T cell in PTX protective groups is significantly reduced at (p < 0.001) in a comparison with I/R group. Spearman's correlation analysis revealed a significant negative correlation between SNHG14 and miR-1206, but a significant positive correlation between SNHG14 and PAG1 in I/R heart tissue. The results indicated that miR-1206 and SNHG14 can be used as biomarkers with perfect sensitivity and specificity. Using PTX reduced cardiac tissue damage. SNHG14 and miR-1206 can be used as a diagnostic tool in I/R.

Expression and gene regulatory network of SNHG1 in hepatocellular carcinoma

BackgroundSmall nucleolar RNA host gene 1 (SNHG1), a long noncoding RNA (lncRNA), is a transcript that negatively regulates tumour suppressor genes, such as p53. Abnormal SNHG1 expression is associated with cell proliferation and cancer. We used sequencing data downloaded from Genomic Data Commons to analyse the expression and interaction networks of SNHG1 in hepatocellular carcinoma (HCC).MethodsExpression was examined using the limma package of R and verified by Gene Expression Profiling Interactive Analysis. We also obtained miRNA expression data from StarBase to determine the lncRNA-miRNA-mRNA–related RNA regulatory network in HCC. Kaplan–Meier (KM) analysis was performed using the survival package of R. Gene Ontology annotation of genes was carried out using Metascape.ResultsWe found that SNHG1 was overexpressed and often amplified in HCC patients. In addition, SNHG1 upregulation was associated with the promotion of several primary biological functions, including cell proliferation, transcription and protein binding. Moreover, we found similar trends of small nucleolar RNA host gene 1 (SNHG1), E2F8 (E2F transcription factor 8), FANCE (FA complementation group E) and LMNB2 (encodes lamin B2) expression. In the SNHG1-associated network, high expression levels of SNHG1 (log-rank P value = 0.0643), E2F8 (log-rank P value = 0.000048), FANCE (log-rank P value = 0.00125) and LMNB2 (log-rank P value = 0.0392) were significantly associated with poor survival. Single-cell analysis showed that E2F8 may play an important role in tumorigenesis or cancer development.ConclusionsOur results highlight the benefit of utilizing multiple datasets to understand the functional potential regulatory networks of SNHG1 and the role of SNHG1 in tumours.

LncRNA SNHG6 Promotes Wilms' Tumor Progression Through Regulating miR-429/FRS2 Axis.

Background: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) has been reported to be an oncogene in a variety of cancers. However, the role of SNHG6 and its associated mechanisms in Wilms' tumor progression remain largely unknown. Methods: The expression of SNHG6, microRNA-429 (miR-429), and FGF receptor substrates 2 (FRS2) messenger RNA (mRNA) was detected by quantitative real-time polymerase chain reaction. Cell proliferation was analyzed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and plate colony assay. The apoptosis was assessed by flow cytometry. Cell glycolytic metabolism was analyzed through detecting the lactate dehydrogenase activity, glucose uptake, lactate production, and ATP level. The target relationship between miR-429 and SNHG6 or FRS2 was predicted by miRcode or Starbase and then validated by dual-luciferase reporter assay and RNA pull-down assay. Murine xenograft model was established to validate the function of SNHG6 in vivo. Results: The level of SNHG6 was elevated in Wilms' tumor tissues and cells, and SNHG6 played an oncogenic role to promote the proliferation and glycolysis and restrain the apoptosis of Wilms' tumor cells. MiR-429 was identified as a target of SNHG6, and miR-429 interference partly reversed the inhibitory effects induced by SNHG6 silencing on the malignant behaviors of Wilms' tumor cells. FRS2 mRNA bound to miR-429 in Wilms' tumor cells. SNHG6 upregulated the expression of FRS2 through acting as a sponge of miR-429. MiR-429-induced influences in Wilms' tumor cells were largely counteracted by the overexpression of FRS2. SNHG6 silencing suppressed the Wilms' tumor growth through miR-429/FRS2 axis in vivo. Conclusion: SNHG6 accelerated Wilms' tumor progression through regulating miR-429/FRS2 signaling in vitro and in vivo.

SP1-induced long non-coding RNA SNHG6 facilitates the carcinogenesis of chondrosarcoma through inhibiting KLF6 by recruiting EZH2

Small nucleolar RNA host gene 6 (SNHG6) is a newly discovered long non-coding RNA (lncRNA), while the regulatory mechanism of SNHG6 in chondrosarcoma is largely unknown. Here we found that SNHG6 expression was upregulated and showed positive correlation with the progression of chondrosarcoma. Functional assays demonstrated that SNHG6 was required for the proliferation, migration, and invasion of chondrosarcoma cells. Mechanistic study revealed that SNHG6 could recruit EZH2 and maintain high level of H3K27me3 to repress the transcription of tumor-suppressor genes, including KLF6. KLF6 was found to bind to the promoter region of SP1 and restrained its transcription, while SP1 could be recruited to the promoter region of SNHG6 and promoted its transcription to form a positive loop. In summary, this study reveals that SP1-induced SNHG6 forms a positive loop to facilitate the carcinogenesis of chondrosarcoma through the suppression of KLF6 by recruiting EZH2, which manifests the oncogenic function of SNHG6 in chondrosarcoma.

LncRNA SNHG3 Promotes Proliferation and Metastasis of Non-Small-Cell Lung Cancer Cells Through miR-515-5p/SUMO2 Axis.

Lung cancer is a global disease and a major cause of cancer-related mortality worldwide. Accumulated studies have confirmed the essential role of long non-coding RNAs (lncRNAs) in the occurrence and development of cancers. Meanwhile, there have been reports concerning the role of Small Nucleolar RNA Host Gene 3 (SNHG3) in various cancers. However, there are so far few studies on the function and mechanism of SNHG3 in lung cancer. In the present study, SNHG3 was found to be highly expressed in lung cancer tissues and cells. Downregulation of SNHG3 could inhibit cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process. In addition, SNHG3 was found to have the ability to bind to miR-515-5p. Furthermore, Small Ubiquitin Like Modifier 2 (SUMO2) was identified to be the downstream target of miR-515-5p, which was negatively correlated with miR-515-5p expression. SNHG3 could positively regulate SUMO2 expression by sponging miR-515-5p. In addition, the rescue experiment showed that simultaneous transfection of miR-515-5p or SUMO2 siRNA could reverse the effect of SNHG3 expression on cell proliferation and metastasis. Collectively, our study demonstrates that SNHG3 can act on miR-515-5p in the form of competitive endogenous RNA (ceRNA) to regulate SUMO2 positively and thus affect the proliferation and metastasis of NSCLC cells. Findings in our study support that SNHG3/miR-515-5p/SUMO2 regulatory axis may become a potential therapeutic target for lung cancer.

Long non-coding RNA small nucleolar RNA host gene 1 alleviates the progression of epilepsy by regulating the miR-181a/BCL-2 axis in vitro

PurposeLong non-coding RNAs (lncRNAs) have been reported to be involved in regulating epilepsy. The purpose of this study is to investigate the possibly regulatory mechanism of small nucleolar RNA host gene 1 (SNHG1) on epilepsy. MethodsQuantitative real-time PCR was utilized to detect the expression of SNHG1, microRNA (miR)-181a, and B-cell lymphoma-2 (BCL-2). Through an enzyme-linked immunosorbent assay, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and cyclooxygenase-2 (COX-2) were determined. The viability and apoptosis of CTX-TNA2 cells were measured using MTT assay and flow cytometry analysis, respectively. Western blot assay was performed to analyze the protein levels of Bcl-2, BCL2-associated X, and Caspase-3. The relationships between miR-181a and SNHG1/BCL-2 were confirmed by the dual-luciferase reporter assay. ResultsSNHG1 expression was down-regulated in EP tissues and kainic acid (KA)-induced CTX-TNA2 cells. The apoptosis and release of inflammatory factors (TNF-α, IL-1β, IL-6, and COX-2) in KA-induced CTX-TNA2 cells were suppressed by SNHG1 overexpression and promoted by miR-181a up-regulation. In addition, we confirmed that SNHG1 targeted miR-181a, whereas BCL-2 was a target gene of miR-181a. Negative correlations between SNHG1 and miR-181a, as well as miR-181a and BCL-2 were exhibited. Both the up-regulation of miR-181a and down-regulation of BCL-2 reversed the inhibiting effects of SNHG1 on apoptosis and inflammatory response of KA-induced CTX-TNA2 cells, and the promoting effect upon cell viability. ConclusionsSNHG1 alleviated the progression of EP by modulating the miR-181a/BCL-2 axis in vitro, thus SNHG1 could act as a possible therapeutic target for treating EP.

Ropivacaine inhibits proliferation, migration, and invasion while inducing apoptosis of glioma cells by regulating the SNHG16/miR-424-5p axis.

BackgroundRegional anesthesia has anti-proliferative and pro-apoptotic effects in various cancers. Therefore, the purpose of this study was to investigate the effects of ropivacaine on the proliferation, migration, invasion, and apoptosis of glioma cells in vitro.MethodsUnder ropivacaine stimulation conditions, proliferation, apoptosis, migration, and invasion of glioma cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), flow cytometry, and transwell assays, respectively. Western blot assay was employed to measure the protein expression levels in glioma cells. The expression levels of small nucleolar RNA host gene 16 (SNHG16) and miR-424-5p were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The interaction relationship between SNHG16 and miR-424-5p was predicted and confirmed using a bioinformatics database and dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays.ResultsAfter treatment with ropivacaine, proliferation, migration, and invasion were repressed while apoptosis was enhanced in glioma cells in a dose-depended manner. In addition, ropivacaine impeded SNHG16 expression in glioma cells. Importantly, overexpression of SNHG16 abolished the ropivacaine-induced effects on glioma cells. Analogously, knockdown of miR-424-5p counteracted the function of ropivacaine in glioma cells. We also found that SNHG16 bound to miR-424-5p and negatively regulated miR-424-5p expression in glioma cells. The rescue experiments indicated that ropivacaine might regulate glioma progression by targeting the SNHG16/miR-424-5p axis.ConclusionOur findings revealed the anti-tumor effects of ropivacaine in glioma by targeting the SNHG16/miR-424-5p axis. These data might extend the understanding of regulatory mechanisms by which ropivacaine could suppress glioma development.

Long noncoding RNA small nucleolar RNA host gene 15 deteriorates liver cancer via microRNA-18b-5p/LIM-only 4 axis.

Extensive studies have explored the involvements of long noncoding RNAs (lncRNAs) in liver cancer. Limitedly, the concrete function of lncRNA small nucleolar RNA host gene 15 (SNHG15) is still elusive. Therefore, the work was initiated to unearth SNHG15-oriented mechanism in liver cancer. Liver cancer tissues were resected. The connection between SNHG15 expression with prognosis and clinicopathological traits of liver cancer patients was evaluated. Liver cancer cells SMMC-7721 were transfected with restored microRNA (miR)-18b-5p or depleted SNHG15 to discover their effects on the proliferation, migration, invasion, cycle arrest, and apoptosis of SMMC-7721 cells. The transfected SMMC-7721 cells were injected into nude mice for further investigation. SNHG15, miR-18b-5p, and LIM-only 4 (LMO4) expressions in tissues and cells were tested. The regulatory connections among SNHG15, miR-18b-5p, and LMO4 were detected. SNHG15 and LMO4 were overexpressed while miR-18b-5p was downregulated in liver cancer tissues and cells. Up-regulated SNHG15 was connected with inferior prognosis and aggressive behaviors of liver cancer patients. SNHG15 knockdown or miR-18b-5p restoration depressed SMMC-7721 cell growth in vivo and in vitro. SNHG15 bound to miR-18b-5p and miR-18b-5p targeted LMO4. The work has illuminated that silencing SNHG15 represses liver cancer progression by modulating miR-18b-5p and LMO4, indicating the therapeutic potency of SNHG15/miR-18b-5p/LMO4 axis in liver cancer.

Dexmedetomidine inhibits microglial activation through SNHG14/HMGB1 pathway in spinal cord ischemia-reperfusion injury mice

Objective Microglial activation is an essential pathological mechanism of spinal cord ischemia-reperfusion injury (SCIRI). Previous studies showed dexmedetomidine (DEX) could alleviate SCIRI while the mechanism was not clear. This study aims to investigate the role of DEX in microglial activation and clarify the underlying mechanism. Methods The motion function of mice was quantified using the Basso Mouse Scale for Locomotion. The expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) was determined by qRT-PCR. The expression of high-mobility group box 1 (HMGB1) was measured by western blot. The activation of microglia was evaluated by the expression of ED-1 and the levels of TNF-α and IL-6. The interplay between SNHG14 and HMGB1 was confirmed with RNA pull-down and RIP assay. The stability of HMGB1 was measured by ubiquitination assay and cycloheximide-chase assay. Results DEX inhibited microglial activation and down-regulated SNHG14 expression in SCIRI mice and oxygen and glucose deprivation/reoxygenation (OGD/R)-treated primary microglia. Functionally, SNHG14 overexpression reversed the inhibitory effect of DEX on OGD/R-induced microglial activation. Further investigation confirmed that SNHG14 bound to HMGB1, positively regulated HMGB1 expression by enhancing its stability. In addition, the silence of HMGB1 eliminated the pro-activation impact of SNHG14 overexpression on DEX-treated microglia under the OGD/R condition. Finally, in vivo experiments showed SNHG14 overexpression abrogated the therapeutic effect of DEX on SCIRI mice by up-regulating HMGB1. Conclusion DEX accelerated HMGB1 degradation via down-regulating SNHG14, thus inhibiting microglial activation in SCIRI mice.

Prognostic Value of Long Noncoding RNA SNHG12 in Various Carcinomas: A Meta-Analysis.

Background Numerous recent studies suggested that overexpression of the long noncoding RNA small nucleolar RNA host gene 12 (SNHG12) exhibited prooncogenic activity in multiple cancers. However, results regarding the prognostic value of SNHG12 in cancers still remained controversial. Therefore, we conducted a meta-analysis complemented with bioinformatics analysis to elucidate the clinical significance of SNHG12 in cancer patients. Methods PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases were searched for eligible studies until July 2020. Additionally, bioinformatics analysis was applied to verify the results of meta-analysis. Results Twenty-three related studies consisting of 1389 cancer patients were enrolled in the current meta-analysis. Elevated SNHG12 expression was found to be significantly associated with poor overall survival (OS) (HR = 1.81; 95% CI: 1.53-2.13; P < 0.001) and disease-free survival (DFS) (HR = 1.40; 95% CI: 1.12-1.76; P = 0.004) in multiple cancers, which were also verified by the results of bioinformatics analysis. Moreover, overexpression of SNHG12 was also related to clinicopathological characteristics including LNM, distant metastasis, high clinical stage, large tumor size, and poor tumor differentiation in diverse types of cancers. Conclusion The present findings indicated that SNHG12 might act as a novel biomarker for diagnosis or prognosis in human cancers.

Long non-coding RNA SNHG15 in various cancers: a meta and bioinformatic analysis

BackgroundThe snoRNA host gene SNHG15 produces a long non-coding RNA (lncRNA) with a short half-life and has been reported to be dysregulated in multiple cancers and has recently been found to be correlated with tumour progression. Therefore, this meta-analysis was performed to evaluate the generalised prognostic role of small nucleolar RNA host gene 15 (SNHG15) in malignancies, based on variable data from different studies.MethodsFour public databases were used to identify eligible studies. The association between prognostic indicators and clinical features was extracted and pooled to estimate the hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was measured using Begg’s test and Egger’s test, and the stability of pooled results were measured using sensitivity analysis. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was screened to further validate our results. Ultimately, we predicted the molecular regulation of SNHG15 based on the public databases.ResultsIn total, 11 studies including 1087 patients were ultimately enrolled in our meta-analysis. We found that SNHG15 overexpression was associated with worse overall survival (OS) and disease-free survival (DFS), and this was validated in the Gene Expression Profiling Interactive Analysis (GEPIA) cohort. Moreover, increased SNHG15 expression suggested advanced TNM stage and LNM, but was not associated with age, gender, or tumour size. No publication bias or instability of the results was observed. SNHG15 was significantly upregulated in seven cancers and elevated expression of SNHG15 indicated shorter OS and DFS in five malignancies based on the validation using the GEPIA cohort. Further functional prediction indicated that SNHG15 may participate in some cancer-related pathways.ConclusionsUpregulation of lncRNA SNHG15 was notably associated with worse prognosis and clinical features, suggesting that SNHG15 might serve as a novel prognostic factor in various cancers.

Long non‑coding RNA SNHG14 affects the proliferation and apoptosis of childhood acute myeloid leukaemiacells by modulating the miR‑193b‑3p/MCL1 axis.

The purpose of the present study was to determine the biological function and associated regulatory mechanism of small nucleolar RNA host gene14 (SNHG14) in childhood acute myeloid leukaemia(AML). SNHG14 expression was measured via RT‑qPCR in bone marrow tissues from 57patients with AML and 57 healthy donors. The clinicopathological features of AML patients with low and high SNHG14 expression were analysed. AML cell viability and apoptosis were assessed using MTT and flow cytometry analyses. The starBase online database, and RNA‑binding protein immunoprecipitation and dual luciferase reporter gene assays were employed to analyse the interactions among SNHG14, microRNA(miR)‑193b‑3p and MCL1 apoptosis regulator BCL2 family member(MCL1). SNHG14 was found to be overexpressed in the bone marrow tissues of patients with AML. The French‑American‑British classification and cytogenetics were significantly different between patients with high and low expression of SNHG14. Silencing SNHG14 decreased AML cell proliferation and facilitated apoptosis. SNHG14 functioned as a sponge for miR‑193b‑3p, and miR‑193b‑3p decreased the viability and accelerated the apoptosis rate of AML cells. In addition, miR‑193b‑3p targeted MCL1. Furthermore, silencing SNHG14 resulted in the sponging of miR‑193b‑3p to regulate cell viability, apoptosis, and MCL1 expression in AML. SNHG14 silencing decreased the viability and promoted apoptosis of AML cells by modulating the miR‑193b‑3p/MCL1 axis.

Long non‑coding RNA SNHG20 promotes colorectal cancer cell proliferation, migration and invasion via miR‑495/STAT3 axis.

Colorectal cancer (CRC) is one of the primary causes of cancer-associated mortality worldwide. However, the potential molecular mechanism of CRC progression remains unknown. Long non-coding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to be involved in the development and progression of a variety of tumors, including CRC. However, the involvement of SNHG20 in CRC progression remains unclear. The aim of the present study was to investigate the functional role and molecular mechanism of SNHG20 in CRC progression. In the present study, SNHG20 expression was found to be significantly upregulated in CRC tissues and cell lines. Association analysis indicated that high SNHG20 expression was significantly association with greater tumor size (P=0.014), tumor invasion depth (P=0.019), positive lymph node status (P=0.022), distant metastasis (P=0.017) and advanced tumor node metastasis stage (P=0.038). Loss-of-function experiments indicated that SNHG20 knockdown could significantly suppress proliferation, migration and invasion in vitro. Notably, SNHG20 knockdown significantly inhibited tumor growth and lung metastasis in vivo. Bioinformatics analysis and luciferase reporter assays confirmed that microRNA (miR)-495 was a direct target of SNHG20. Rescue assays indicated that miR-495 inhibitor reversed the suppressive effects of SNHG20 knockdown on CRC progression. Moreover, STAT3 was identified as a downstream target of miR-495 in CRC. STAT3 overexpression partially rescued the inhibitory effects of SNHG20 knockdown on CRC progression. Taken together, the results revealed that SNHG20 facilitated CRC progression by regulating STAT3 expression and by sponging miR-495.

SNHG1 Promotes Malignant Progression of Glioma by Targeting miR-140-5p and Regulating PI3K/AKT Pathway.

PurposeTo explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma.Materials and MethodsThe expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed.ResultsSNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR-140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and si-SNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression.ConclusionSNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma.