Non-coding RNA SNHG1 Research Articles

Long noncoding RNA SNHG15 serves as an oncogene and predicts poor prognosis in epithelial ovarian cancer.

ObjectiveThis study aims to investigate the functional role of long noncoding RNA SNHG15 in epithelial ovarian cancer (EOC).Materials and methodsThe expression of SNHG15 was measured in EOC cells and tissues using qRT-PCR. The correlation of SNHG15 expression and the clinicopathological characters was statistically analyzed. The prognosis of patients with different clinical features in the high/low SNHG15 expression groups were calculated. Moreover, univariate and multivariate Cox regression analyses were performed to identify the risk factors for poor overall survival (OS) and progression-free survival (PFS). The effect of SNHG15 on the migration and invasion was evaluated using Transwell and Matrigel, respectively. The proliferation ability of EOC cells was tested using colony formation and MTT assay. The influence of SNHG15 on the cisplatin resistance was detected by measuring cell inhibition rate and cell viability.ResultsSNHG15 was upegulated in EOC cells and tissues. High SNHG15 expression was correlated with EOC progression and predicted poor OS and PFS in different subgroups of EOC patients. Moreover, multivariate Cox regression analysis defined high SNHG15 expression as an independent risk factor for poor OS and PFS. Furthermore, functional assays showed that the overexpression of SNHG15 promoted migration and invasion, while the loss of SNHG15 suppressed migration and invasion. Furthermore, the proliferation of EOC cells was improved after the ectopic expression of SNHG15, which was suppressed with SNHG15 deficiency. In addition, cisplatin-resistant EOC cells were established for detecting the effect of SNHG15 on EOC chemoresistance. The results showed that cisplatin-resistant EOC cells exhibited much higher levels of SNHG15 expression than controls, and SNHG15 contributed to the chemoresistance of EOC cells.ConclusionThis study confirms that SNHG15 contributes to the migration, invasion, proliferation, and chemoresistance of EOC. SNHG15 may serve as a potential therapeutic target and prognostic biomarker of EOC patients.

Up-regulation of long non-coding RNA SNHG6 predicts poor prognosis in renal cell carcinoma.

We aim to investigate the expression of long non-coding RNA SNHG6 and analyze its clinicopathological significance in renal cell carcinoma (RCC). A total of 81 cases of RCC tissues were collected and enrolled. Total RNA was extracted using the TRIzol method followed by qRT-PCR detection of the mRNA level of SNHG6. The x2-test was used to analyze the correlation between SNHG6 expression and clinicopathological variables, including age, gender, TNM stage, Fuhrman grade, tumor size, and overall prognosis. Kaplan-Meier survival curve was plotted to analyze the association between SNHG6 expression and overall survival. Univariate and multivariate analysis were carried out with the Cox proportional hazard analysis. SNHG6 was shown to be markedly upregulated in RCC tissues as compared with normal controls. Elevated SNHG6 was found to significantly correlate with clinical stage, lymph node metastasis, Fuhrman grade, and tumor size (p<0.05). Kaplan-Meier survival analysis exhibited that elevated SNHG6 was remarkably associated with poor overall survival (p<0.001). Moreover, multivariate analysis revealed that SNHG6 expression was an independent prognostic factor in RCC. We showed that up-regulated SNHG6 was significantly associated with tumor progression and was an independent prognostic factor in RCC, suggesting that SNHG6 can work as a promising prognostic predictor in RCC.

LncRNA SNHG1 alleviates OGD induced injury in BMEC via miR-338/HIF-1α axis

BackgroundBrain microvascular endothelial cell (BMEC) is an important therapeutic target for the inhibition of brain vascular dysfunction in ischemic stroke. Expression of long non-coding RNA SNHG1 is reportedly upregulated in BMEC after OGD. The present study aims to investigate the potential roles of SNHG1 in OGD-induced injury in BMEC. MethodsMice primary brain microvascular endothelial cells (BMEC) were cultured under “normal” or “oxygen/glucose-deprived” (OGD) conditions. The expression of SNHG1 and miR-338 after OGD were examined by qPCR. shRNA against SNHG1 was used to knockdown SNHG1 in BMEC. MiR-338-3p mimic and inhibitor were used to change the expression of miR-338 in BMEC. The relationship between SNHG1 and miR-338, and the relationship between miR-338 and HIF-1α were clarified using RNA pull-down and luciferase reporter gene assays, respectively. ResultsSNHG1 and miR-338 were upregulated in OGD induced BMEC. SNHG1 silence aggravated OGD-induced cell apoptosis by down-regulating Bcl-2, HIF-1α and VEGF-A, and upregulating caspase 3 activity and Bax. MiR-338 was upregulated in SNHG1-silenced BMEC. RNA pull-down assays showed that SNHG1 could be directly bound by miR-338. In addition, miR-338 overexpression reduced cell viability in OGD while miR-338 inhibition protected BMEC against OGD-induced injury. Furthermore, luciferase reporter assay showed that HIF-1α was a direct target of miR-338. ConclusionsSNHG1 exerted protective effects against OGD induced injury via sponging miR-338, thus upregulating HIF-1α/VEGF-A in BMEC.

LncRNA SNHG7 promotes development of breast cancer by regulating microRNA-186.

To elucidate the biological functions of long non-coding RNA (lncRNA) SNHG7 in breast cancer (BC), and its underlying mechanism in the occurrence and progression of BC. The expression of SNHG7 in 72 pairs of BC tissues and paracancerous tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Correlation between SNHG7 expressions with pathological indicators of BC patients was analyzed. Similarly, SNHG7 expression in BC cell lines was determined by qRT-PCR as well. After constructing the small inference RNA of SNHG7, cell proliferation, migration and invasion were determined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assay. MicroRNA-186 expression in BC tissues and cells was accessed. Dual-luciferase reporter gene assay was conducted to verify the binding condition between SNHG7 and microRNA-186. SNHG7 expression was higher in BC tissues than that of paracancerous tissues. High expression of SNHG7 was positively correlated to tumor stage, lymph node metastasis and distant metastasis, whereas not correlated to age, sex and tumor location of BC. Kaplan-Meier curves revealed that higher expression of SNHG7 is correlated to the worse prognosis of BC patients. SNHG7 was highly expressed in BC cells as well. Knockdown of SNHG7 inhibited proliferative, invasive and migratory abilities of BC cells. QRT-PCR data showed that microRNA-186 is lowly expressed in BC tissues compared with that of paracancerous tissues. MicroRNA-186 was lowly expressed in BC cells as well. Both mRNA and protein levels of microRNA-186 were negatively correlated to SNHG7 in BC tissues. Finally, the dual-luciferase reporter gene assay demonstrated that SNHG7 could be directly targeted by microRNA-186. SNHG7 is highly expressed in BC, which is correlated to tumor stage, lymph node metastasis and distant metastasis of BC patients. SNHG7 could promote malignant progression of BC by regulating microRNA-186.

Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer.

Long noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value. Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT-PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc-small-nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set. Furthermore, in the expanded validation set, high expression of lnc-SNHG15 was significantly associated with lymph-node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA-SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003). Multivariate analyses demonstrated that lncRNA-SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Cox's regression: 2.731). Lnc-SNHG15 overexpression was significantly associated with CLM and high-expression of lnc-SNHG15 in CRC was an independent predictor of poor survival.

Increased expression of long non-coding RNA SNHG16 correlates with tumor progression and poor prognosis in non-small cell lung cancer

In this study, we report that lncRNA SNHG16 is upregulated in non-small cell lung cancer (NSCLC) tissues, and correlates with tumor size, TNM stage and lymph node metastasis. Kaplan-Meier analysis shows that the patients with high SNHG16 expression have poorer disease-free survival (DFS) and overall survival (OS) than the patients with low SNHG16 expression. Multivariate Cox regression analysis reveals that SNHG16 expression could be regarded as an independent predictor for DFS and OS in NSCLC patients. Cell experiments show that SNHG16 promotes NSCLC cell proliferation, migration and invasion. miR-146a is further identified and confirmed to be the target of SNHG16, and SNHG16 functions by targeting miR-146a. Subsequently, MUC5AC, a major mucin in the human respiratory tract correlated with post-operative metastasis and recurrence of NSCLC, is confirmed to be regulated by SNHG16 and miR-146a, and plays a positive role in promoting cell proliferation, migration and invasion, which might be involved in the oncogenic activity of SNHG16-miR-146a axis in NSCLC. Animal experiments also confirm these conclusions. Collectively, these results elucidate a potential mechanism underlying the carcinogenesis role of SNHG16 in NSCLC, and indicate that SNHG16 could act as a novel promising marker for prognosis, and a potential therapeutic target for NSCLC treatment.

Identification of oncogenic long noncoding RNA SNHG12 and DUXAP8 in human bladder cancer through a comprehensive profiling analysis.

Bladder cancer is a common urological malignancies world-wide. Recently, a growing number of evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. However, the expression pattern of lncRNAs in bladder cancer and their underlying function remain poorly understood. To identify lncRNAs profile alterations and uncover valuable lncRNA candidates for bladder cancer diagnostic, we conducted a comprehensively lncRNAs profiling analyses and explored their clinical relevance using The Cancer Genome Atlas (TCGA) data and three independent microarray profiling data from the Gene Expression Omnibus (GEO). After annotation and analyses of these data, we found that lots of lncRNAs were dysregulated in bladder specimen when compared with normal control specimen. In addition, we found that differential expression of these lncRNAs is accompanied by genomic variations, including genome loci copy number deletion or amplification. Importantly, a part of these lncRNAs are related to bladder cancer patients outcome, such as SNHG10, SNHG12 and LINC00115. Finally, we validated two of these lncRNAs' (DUXAP8 and SNHG12) function in bladder cancer cells by down-regulating their expression with siRNAs, and found that down-regulation of DUXAP8 and SNHG12 could inhibit bladder cancer cells proliferation in vitro. In summary, this study demonstrated that a lot of lncRNAs are dysregulated in bladder cancer, and might provide useful lncRNAs resource for potential prognostic or diagnostic markers for this disease.

Evaluating the diagnostic and prognostic value of long non-coding RNA SNHG15 in pancreatic ductal adenocarcinoma.

Long non-coding RNA SNHG15 (SNHG15) has been reported to play very important roles in the malignancy behaviors of various tumors, including pancreatic ductal adenocarcinoma (PDAC). However, its clinical significance in PDAC remains largely unclear. The aim of this study was to investigate whether the aberrant expression of SNHG15 can be used as potential prognostic and diagnostic markers of human PDAC. TaqMan Real Time-PCR was performed to investigate the expression of SNHG15 in PDAC tissues and serum samples. Receiver operator characteristic (ROC) analysis was applied to obtain the diagnostic utility of SNHG15. Association between SNHG15 levels and clinicopathological factors was analyzed. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. SNHG15 levels were significantly up-regulated in both sera and tumors tissues from PDAC patients. ROC curve analysis revealed that SNHG15 may be a potential biomarker for differentiating PDAC tissues from normal pancreatic tissues, and the plasma levels of SNHG15 may be a potential biomarker for differentiating PDAC patients from healthy controls. Clinicopathologic analysis revealed that high SNHG15 expression was associated with tumor differentiation (p = 0.000), lymph node metastasis (p = 0.001) and tumor stage (p = 0.005). Furthermore, patients with high SNHG15 expression had a shorter overall survival compared with the low SNHG15 expression group (p = 0.003). Also, Cox multivariate analyses confirmed that SNHG15 expression was an independent prognostic factor in PDAC (p < 0.004). Our study firstly indicated the potential value of SNHG15 as an important biomarker for the diagnosis and prognosis prediction of PDAC.

Long noncoding RNA SNHG6 promotes the progression of colorectal cancer through sponging miR-760 and activation of FOXC1.

BackgroundColorectal cancer (CRC) is one of most common cancers worldwide. Long non-coding RNA SNHG6 has been reported to act as essential regulators in several cancers. However, the functional role and molecular mechanism of SNHG6 in colorectal cancer remain unclear.MethodsQuantitative real-time polymerase chain reaction (PCR) was performed to evaluate the SNHG6 expression in CRC tissues. Colony formation, transwell assays and in vivo mice models were carried out to assess the effect of SNHG6 on CRC biological functions.ResultsIn the present study, we showed that the expression of SNHG6 was significantly upregulated in CRC tissues and cell lines. High expression of SNHG6 was associated with shorter overall survival in CRC patients. Functionally, SNHG6 knockdown significantly inhibited cell proliferation, invasion and migration both in vitro and in vivo. Mechanically, miR-760 was a direct target of SNHG6, and repression of miR-760 could rescue the inhibitory effect of SNHG6 knockdown on CRC progression. In addition, SNHG6 positively regulated FOXC1 expression through sponging miR-760 in CRC cells, thus indicating that SNHG6 exerted an oncogenic role in CRC by acting as a ceRNA of miR-760.ConclusionOur results indicate that long non-coding RNA SNHG6 promotes colorectal cancer progression by sequestering miR-760 and activating FOXC1, our findings suggest that SNHG6 may serve as a potential therapeutic target for CRC.

Long noncoding RNA SNHG16 reduced ketamine-induced neurotoxicity in human embryonic stem cell-derived neurons

BackgroundClinical evidence demonstrates that prolonged exposure to ketamine may cause irreversible injury to immature human brains. In this study, we utilized an in vitro model to examine the function of long noncoding RNA (lncRNA) SNHG16 in ketamine-induced neurotoxicity in human embryonic stem cell (hESC)-derived neurons. MethodsHESCs were induced toward neuronsin vitro, and treated with ketamine, at various concentrations, for 48 h. Viability, apoptosis, caspase-3 activity and ROS activity were then examined among hESC-derived neurons. Ketamine-induced gene expression change of SNHG16 was assessed by qRT-PCR. SNHG16 was overexpressed in hESC-derived neurons, which were then treated with ketamine, followed by biochemical assays to assess the effects of SNHG16 upregulation on ketamine-induced neurotoxicity. Correlation between SNHG16 and NeuroD1 gene was assess by qRT-PCR. In SNHG16-upregulated hESC-derived neurons, they were double transfected with siRNA to knock down NeuroD1. The functions of NeuroD1 inhibition on SNHG16-associated neural protection on ketamine-induced neurotoxicity were further assessed. Results48-h in vitro treatment of ketamine induced significant neurotoxicity, and downregulated SNHG16 among hESC-derived neurons. Conversely, SNHG16 upregulation reduced ketamine-induced neurotoxicity. NeuroD1 expression was downregulated by ketamine in hESC-derived neurons, and concomitantly upregulated by SNHG16 overexpression. SiRNA-mediated NeuroD1 inhibition reversed the protection of SNHG16 upregulation on ketamine-induced neurotoxicity. ConclusionsSNHG16 is an important epigenetic factor which may functionally modulate ketamine-induced neurotoxicity through NeuroD1.

The long non-coding RNA SNHG5 regulates gefitinib resistance in lung adenocarcinoma cells by targetting miR-377/CASP1 axis.

Gefitinib resistance is one of the major obstacles for the treatment of lung adenocarcinoma (LAD). The present study aimed to investigate the effects of the long non-coding RNA (lncRNA), small nucleolar RNA host gene 5SNHG5 on gefitinib resistance in LAD and explore the underlying mechanisms. The quantitative real-time PCR (qRT-PCR) results showed that SNHG5 expression was significantly down-regulated in LAD patients with acquired gefitinib resistance and gefitinib resistant LAD cell lines. SNHG5 overexpression sensitized gefitinib resistant LAD cells to gefitinib treatment, while knockdown of SNHG5 rendered gefitinib sensitive LAD cells to gefitinib treatment. Bioinformatics analysis showed that SNHG5 exerted its function through interaction with miR-377, which was further confirmed by luciferase reporter assay in 293T cells. Overexpression of SNHG5 suppressed the expression of miR-377, while the knockdown of SNHG5 increased the miR-377 expression. MiR-377 expression was significantly up-regulated in LAD specimens with acquired gefitinib resistance and was negatively correlated with SNHG5 expression. In addition, CASP1 was predicted as a downstream target of miR-377. Overexpression of miR-377 suppressed the expression of CASP1 in PC9 cells and knockdown of miR-377 increased the CASP1 expression in PC9GR cells. In vitro functional assay showed that knockdown of CASP1 in SNHG5-overexpressed PC9GR cells abolished their gefitinib resistance. Overall, the present study demonstrated, for the first time, that the SNHG5/miR-377/CASP1 axis functions as an important role in LAD cells gefitinib resistance and potentially contributes to the improvement of LAD diagnosis and therapy.

LncRNA SNHG12 inhibits miR-199a to upregulate SIRT1 to attenuate cerebral ischemia/reperfusion injury through activating AMPK signaling pathway

Cerebral ischemia caused severe disability, and associated with a series of neurological events. Long non-coding RNA SNHG12 was found to be upregulated in mouse brain microvascular endothelial cells by cerebral ischemia. Moreover, it was reported that SNHG12 could directly interact with miR-199a and sirtuin 1 (SIRT1) as a direct target of miR-199a in other diseases. However, the function and mechanism of SNHG12 in cerebral ischemia and reperfusion (I/R) injury of neuronal cells remains unclear. The present study was thus designed to explore the potential effect of SNHG12 and to investigate the underlying mechanism in I/R neuronal cells. we found thatSNHG12 was upregulated in primary neuronal cells and N2a cells and peaked at 12 h and 24 h after OGD/R treatment, respectively. Meanwhile, MTT assay showed that knockdown SNHG12 inhibited cell proliferation under OGD/R condition. And flow cytometry analyses revealed more apoptosis rate was caused by SNHG12 knockdown. Mechanistically, SNHG12 interacted with miR-199a and decreased the expression of miR-199a. Overexpression miR-199a largely inhibited the cell proliferation and induced the cell apoptosis. Meanwhile, SNHG12 was proven to target miR-199a and then activated SIRT1 expression, which finally led to activation of AMPK signaling pathway.In summary, we demonstrate SNHG12 targets miR-199a to upregulate SIRT1 expression, which attenuates cerebral ischemia/reperfusion injury through AMPK pathway activation. Our findings provide molecular mechanism by which SNHG12 attenuates cerebral I/R injury and facilitate development of therapeautical strategies for treating ischemia-induced stroke.

Gene Amplification Driven-Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small Cell Lung Cancer

Background: Lung cancer is the most common cancer all around the world with high morbidity and mortality. Long non-coding RNA(LncRNA) has been reported to be a critical role in non-small cell lung cancer (NSCLC) proliferation and migration. Methods: In the present study, we analyzed the TCGA data to figure out the expression of SNHG17 in NSCLC. RACE was used to acquired the exact sequence of SNHG17. We modulated SNHG17 expression by RNA interference and a series of functional assays such as MTT, transwell and EdUstaining assays were performed. Flow cytometry was used to explore the involvement of SNHG17 in NSCLC cell apoptosis The global gene expression profile regulated by SNHG17 in NSCLC cells was acquired through RNA-Seq assays and several potential downstream genes were confirmed by qRT-PCR. Results: We found that lncRNA SNHG17 was up-regulated in NSCLC driven by the amplification ofcopy number,indicating the special role of SNHG17 in NSCLC.Full exact length of SNHG17 was determined. Knockdown of SNHG17 inhibited proliferation, migration and promoted apoptosis of NSCLC cells. We acquired the global gene expression profile regulated by SNHG17 in A549. We found 637 genes were up-regulated while 581 genes were down-regulated. We selected three genes(FOXA1, XAF1, BIK) which were closely releated to proliferation and apoptosis and confirmed their altered expression in A549 and PC-9 treated by si-SNHG17. Conclusion: Our findings indicated gene amplification driven-long noncoding RNA SNHG17 promotes cell proliferation and migration in NSCLC,suggesting its potential value as biomarker in NSCLC. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81672307, 81703056, 81702266;), the Medical Innovation Team Foundation of the Jiangsu Provincial Enhancement Health Project (No. CXTDA2017021), the “333 high class Talented Man Project” (No.BRA2016509), China Postdoctoral Science Foundation (2017M610339) and Jiangsu Planned Projects for Postdoctoral ResearchFunds (1701041A). Declaration of Interest: None.

Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression

BackgroundColorectal cancer (CRC) arises in a multistep molecular network process, which is from either discrete genetic perturbation or epigenetic dysregulation. The long non-coding RNAs (lncRNAs), emerging as key molecules in human malignancy, has become one of the hot topics in RNA biology. Aberrant O-glycosylation is a well-described hallmark of many cancers. GALNT7 acts as a glycosyltransferase in protein O-glycosylation, involving in the occurrence and development of CRC.MethodsThe microarrays were used to survey the lncRNA and mRNA expression profiles of primary CRC cell line SW480 and metastatic CRC cell line SW620. Cell proliferation, migration, invasion, and apoptosis were assayed. Xenograft mouse models were used to determine the role of lncRNA-SNHG7 in CRC in vivo. In addition, CNC analysis and competing endogenous analysis were used to detect differential SNHG7 and relational miRNAs expression in CRC cell lines.ResultsSNHG7 expression showed a high fold (SW620/SW480) in CRC microarrays. The CRC patients with high expression of SNHG7 had a significantly poor prognosis. Furthermore, SNHG7 promoted CRC cell proliferation, metastasis, mediated cell cycle, and inhibited apoptosis. SNHG7 and GALNT7 were observed for co-expression by CNC analysis, and a negative correlation of SNHG7 and miR-34a were found by competing endogenous RNA (ceRNA) analysis. Further results indicated that SNHG7 facilitated the proliferation and metastasis as a competing endogenous RNA to regulate GALNT7 expression by sponging miR-34a in CRC cell lines. SNHG7 also played the oncogenic role in regulating PI3K/Akt/mTOR pathway by competing endogenous miR-34a and GALNT7.ConclusionThe CRC-related SNHG7 and miR-34a might be implicated in CRC progression via GALNT7, suggesting the potential usage of SNHG7/miR-34a/GALNT7 axis in CRC treatment.

Epigenetic silencing of tumor suppressor gene CDKN1A by oncogenic long non-coding RNA SNHG1 in cholangiocarcinoma

Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA. As revealed by our data, SNHG1 knockdown extensively inhibited CCA cell migration as well as proliferation in vitro and in vivo. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. These data verified a major function of the epigenetic regulation of SNHG1 in CCA oncogenesis, in addition to its likely function as a target for CCA interruption.

Upregulated long noncoding RNA Snhg1 promotes the angiogenesis of brain microvascular endothelial cells after oxygen-glucose deprivation treatment by targeting miR-199a.

Angiogenesis after ischemic stroke has important clinical significance, which stimulates endogenous recovery mechanisms and improves the neurological outcome. Enhancing angiogenesis may facilitate the function recovery from ischemic stroke. Recent studies have shown that aberrant expression of long noncoding RNAs (lncRNAs) is related to angiogenesis after ischemic stroke. Snhg1, a cancer-related lncRNA, has been reported to be upregulated after stroke. However, little is known about its role in stroke. In this study, we performed in vitro experiments to investigate the effects of Snhg1 on cell survival and angiogenesis and molecular mechanism in ischemic stroke. Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemia/reperfusion injury in vitro. Sngh1 was increased in brain microvascular endothelial cells (BMECs) with the prolongation of exposure to OGD, and promoted BMEC survival under OGD/R condition, and angiogenesis after OGD/R treatment. miR-199a was identified and validated to be a direct target of Snhg1, and function effects of Snhg1 on BMEC survival and angiogenesis depended on miR-199a, which is involved in the regulation of hypoxia inducible factor and vascular endothelial cell growth factor expression. These findings contribute to a better understanding of the pathogenesis of ischemic stroke and facilitate the development of proangiogenesis therapy for this disease.

Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p.

Glioma is the most common primary brain tumor. The small nucleolar RNA host gene (SNHG) SNHG6 is a potential oncogene in the development of several types of cancers. In this study, we investigated the functional role of long non-coding RNA (lncRNA) SNHG6 in the malignancy of glioma in cell lines and transplanted nude mice. We found that the expression of lncRNA SNHG6 was higher in glioma tissues and cells than in normal brain tissues and cells. The expression of lncRNA SNHG6 was positively correlated with the malignancy and poor prognosis of glioma patients. microRNA (miR)-101-3p expression was decreased in glioma tissues and cells and was negatively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of lncRNA SNHG6 was negatively correlated with the expression of miR-101-3p. SNHG6 contained a binding site of miR-101-3p. Knockdown of SNHG6 expression resulted in a significant increase of miR-101-3p expression. miR-101-3p mimic markedly decreased the luciferase activity of SNHG6. Knockdown of SNHG6 inhibited glioma cell proliferation, migration, and epithelial-mesenchymal transition (EMT), and increased apoptosis. miR-101-3p mimic enhanced knockdown of SNHG6-induced inhibition of cell proliferation, migration, and EMT, and an increase of apoptosis. Anti-miR-101-3p reversed the the effects of si-SNHG6 on cell malignancy. Knockdown of SNHG6 remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of SNHG6 increased the expression of miR-101-3p and reduced EMT biomarker expression. Our study provides novel insights into the functions of lncRNA SNHG6/miR-101-3p axis in the tumorigenesis of glioma.

LncRNA SNHG7 promotes the proliferation of esophageal cancer cells and inhibits its apoptosis.

Our research studied the expression of long noncoding RNA (lncRNA) SNHG7 in esophageal cancer cells and tissues. The effect of lncRNA SNHG7 on proliferation and apoptosis of esophageal cancer cells has been discussed. Si-SNHG7 was transfected into esophageal cancer cells, and qRT-PCR was performed to detect the expression of lncRNA SNHG7 in esophageal cancer cells and tissues. The effect of SNHG7 on the proliferation of esophageal cancer cells was measured by CCK8 assay and plate cloning assay, respectively. Flow cytometry was used to detect the effect of SNHG7 on the cell cycle and apoptosis rate of esophageal cancer cells. Changes in expression of downstream protein p15 and p16 after si-SNHG7 intervention were analyzed by qRT-PCR and Western blot. QRT-PCR showed that the expression of SNHG7 in esophageal cancer tissues and cells was significantly up-regulated. After the si-SNHG7 intervention, the proliferation of esophageal cancer cells was inhibited, the apoptosis rate increased, and the cell cycle was blocked in G1-G0 phase. QRT-PCR and Western blot showed that, after the si-SNHG7 intervention, the expression of p15 and p16 increased significantly. The expression of SNHG7 in the tissues and cells of esophageal cancer is significantly up-regulated. SNHG7 can partly promote the development of esophageal cancer by regulating the expression of p15 and p16.

Mo1375 - Long Non-Coding RNA Snhg1 Affects Cell Proliferation and Migration by Epigenetically Regulating IL11 and CDKN1A Expression in Cholangiocarcinoma

Mo1375 - Long Non-Coding RNA Snhg1 Affects Cell Proliferation and Migration by Epigenetically Regulating IL11 and CDKN1A Expression in Cholangiocarcinoma

Long non-coding RNA SNHG14 contributes to gastric cancer development through targeting miR-145/SOX9 axis.

This study aimed to elucidate the roles of long non-coding RNA SNHG14 in gastric cancer development. LncRNA SNHG14 was markedly up-regulated in gastric cancer tissues and cells. Knockdown of SNHG14 significantly inhibited SGC-7901 cell viability, migration, invasion, and promoted cell apoptosis. In addition, miR-145 was negatively regulated by SNHG14 and the effects of SNHG14 knockdown on cell viability, apoptosis, migration, invasion, and the expression of apoptosis-related proteins and EMT-markers were reversed by inhibition of miR-145 at the same time. Furthermore, SOX9 was verified as a functional target of miR-145, and miR-145 regulated tumor malignant behaviors through regulating SOX9. Besides, knockdown of SNHG14 inhibited the expression of p-PI3 K, p-AKT, and p-mTOR and promoted PTEN expression, where miR-145 inhibition had opposite effects. Moreover, the activated PI3 K/AKT/mTOR pathway caused by miR-145 inhibition was counteracted after knockdown of SOX9. Our findings indicate that up-regulation of lncRNA SNHG14 may contribute to gastric cancer development via targeting miR-145/SOX9 axis and involving in PI3 K/AKT/mTOR pathway. SNHG14-miR-145/SOX9 axis may be a promising therapeutic strategy for gastric cancer treatment.