Role Of Small Nucleolar RNA Host Gene 1 Research Articles

LncRNA SNHG6 promotes glycolysis reprogramming in hepatocellular carcinoma by stabilizing the BOP1 protein

ABSTRACT Metabolic reprogramming is an important feature in tumor progression. Long noncoding RNA’s (lncRNA) small nucleolar RNA host gene 6 (SNHG6) acts as a proto-oncogene in hepatocellular carcinoma (HCC) but its role in glycolysis is mostly unknown. The role of SNHG6 and Block of proliferation 1 (BOP1) on glycolysis is assessed by glucose uptake, lactate production, oxygen consumptive rate (OCR) and extracellular acidification rate (ECAR) and glycolytic enzyme levels. The regulatory effect of SNHG6 on BOP1 protein was confirmed by Western blotting, MS2 pull-down, RNA pull-down, and RIP assay. SNHG6 and BOP1 levels were increased in HCC tissues and cells. SNHG6 and BOP1 were prognostic factors in HCC patients and significantly correlated to TP53 mutant and tumor grade. SNHG6 promoted proliferation, inhibited apoptosis, enhanced glucose uptake and lactate production, decreased OCR, and increased ECAR in HCC cell lines. SNHG6 could bind the BOP1 protein and enhance its stability. BOP1 overexpression rescued the change of proliferation, apoptosis, and glycolysis in HCCLM3 and SMMC-7721 cells. Our data indicate that SNHG6 accelerates proliferation and glycolysis and inhibits the apoptosis of HCC cell lines by binding the BOP1 protein and enhancing its stability. Both SNHG6 and BOP1 are promising prognostic and therapeutic markers in HCC.

Positive feedback loop of lncRNA SNHG1/miR‑16‑5p/GATA4 in the regulation of hypoxia/reoxygenation‑induced cardiomyocyte injury.

Numerous studies have demonstrated that long non-coding RNAs (lncRNAs) serve an important regulatory role in ischemic injury of cardiomyocytes. lncRNA small nucleolar RNA host gene 1 (SNHG1) could effectively protect cardiomyocytes against various injuries. However, the role of SNHG1 in ischemic cardiomyocyte injury is unclear. It was hypothesized that SNHG1 may have a protective effect on cardiomyocyte injury induced by hypoxia/reoxygenation (H/R) by sponging microRNA (miRNA/miR). The purpose of the present study was to explore the role and molecular mechanism of SNHG1 in ischemic cardiomyocyte injury. A H9c2 cardiomyocyte H/R model was established. The expression levels of SNHG1 in cardiomyocytes treated with H/R were detected using reverse transcription-quantitative PCR. A luciferase reporter assay was used to analyze the associations among SNHG1, miR-16-5p and GATA binding protein 4 (GATA4). Chromatin immunoprecipitation experiments were performed to analyze the interaction between SNHG1 and GATA4. Cell Counting Kit-8, enzyme-linked immunosorbent assay, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling and western blotting experiments were used to detect cell activity, lactate dehydrogenase release, apoptosis and apoptosis-related proteins (Bcl-2, Bax, Cleaved caspase-3 and Cleaved caspase-9), respectively. The expression levels of SNHG1 were downregulated in cardiomyocytes treated with H/R. Overexpression of SNHG1 had a protective effect on cardiomyocyte injury induced by H/R. In addition, SNHG1 could regulate the expression levels of GATA4 via sponging of miR-16-5p. Further experiments revealed that GATA4 could bind to the promoter region of SNHG1 and subsequently regulated the expression levels of SNHG1, indicating the important role of the positive feedback loop of SNHG1/miR-16-5p/GATA4 in cardiomyocyte ischemic injury. To conclude, the present study revealed the protective effect of the SNHG1/miR-16-5p/GATA4 positive feedback loop on cardiomyocyte injury induced by H/R and provided a potential therapeutic target for ischemic cardiomyocyte injury.

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.

Long non-coding RNA SNHG6 regulates the sensitivity of prostate cancer cells to paclitaxel by sponging miR-186

BackgroundChemo-resistance is one of the main obstacles in the treatment of prostate cancer (PCa). Long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) is involved in the chemo-resistance of various tumors. We aim to survey the role and underlying molecular mechanism of SNHG6 in PCa resistance to paclitaxel (PTX).MethodsThe expression of SNHG6 and miR-186 was detected using quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, and apoptosis of PTX-resistant PCa cells were determined via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), transwell assay, or flow cytometry assay. Protein levels of CyclinD1, matrix metalloproteinase 9 (MMP9), Vimentin, E-cadherin, Cleaved-caspase-3 (Cleaved-casp-3) Cleaved-caspase-9 (Cleaved-casp-9), Multidrug Resistance associated Protein 1 (MRP1), and multidrug resistance-1 (MDR1) were assessed by western blot analysis. The relationship between SNHG6 and miR-186 were confirmed by dual-luciferase reporter assay. The role of SNHG6 in vivo was confirmed by xenograft tumor model.ResultsSNHG6 expression was increased and miR-186 expression was reduced in drug-resistant PCa tissues and cells. SNHG6 knockdown elevated PTX-resistant PCa cells sensitivity to PTX in vitro and in vivo, and repressed proliferation, migration, and invasion of PTX-resistant PCa cells in vitro. Importantly, SNHG6 acted as a sponge of miR-186. Furthermore, miR-186 downregulation reversed SNHG6 silencing-mediated cell sensitivity to PTX, proliferation, migration, and invasion in PTX-resistant PCa cells.ConclusionsSNHG6 knockdown elevated the sensitivity of PTX-resistant PCa cells to PTX by sponging miR-186, indicating that SNHG6 might be a therapeutic target for PCa.

LncRNA SNHG1 contributes to the regulation of acute myeloid leukemia cell growth by modulating miR-489-3p/SOX12/Wnt/β-catenin signaling.

The long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) is a critical regulator for the development and progression of multiple tumors. Yet, the role of SNHG1 in acute myeloid leukemia (AML) is unknown. The present study demonstrated that SNHG1 expression was upregulated in AML. SNHG1 silencing markedly repressed AML cell growth, whereas SNHG1 overexpression had the opposite effect. MicroRNA-489-3p (miR-489-3p) was identified as a SNHG1-targeting miRNA. SNHG1 knockdown increased miR-489-3p expression. Low expression of miR-489-3p was correlated with high expression of SNHG1 in AML tissues. miR-489-3p overexpression restricted AML cell growth, and SRY-related high-mobility-group box 12 (SOX12) was identified as a miR-489-3p-targeting gene. SNHG1 inhibition or miR-489-3p overexpression inactivated Wnt/β-catenin signaling through downregulation of SOX12. SOX12 overexpression partially reversed the SNHG1 knockdown- or miR-489-3p overexpression-mediated effects. Taken together, these data indicate that suppression of SNHG1 downregulates AML cell growth by inactivating SOX12/Wnt/β-catenin signaling via upregulating miR-489-3p.

Long non-coding RNA small nucleolar RNA host gene 6 aggravates pancreatic cancer through upregulation of far upstream element binding protein 1 by sponging microRNA-26a-5p.

BackgroundPancreatic cancer (PC) is a highly deadly malignancy with few effective therapies. We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) plays in PC cells by targeting far upstream element binding protein 1 (FUBP1) via microRNA-26a-5p (miR-26a-5p).MethodsSNHG6 expression was predicted by bioinformatics, followed by verification via reverse transcription quantitative polymerase chain reaction. Then, the interactions among SNHG6, miR-26a-5p, and FUBP1 were detected through online software analysis, dual luciferase reporter assay and RNA pull-down. After that, cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6, miR-26a-5p, and FUBP1 and their roles in PC cells. Finally, the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice. A t-test, one-way and two-way analysis of variance were used for data analysis.ResultsCompared with that in normal tissues, SNHG6 was highly expressed in PC tissues (1.00 ± 0.05 vs. 1.56 ± 0.06, t = 16.03, P < 0.001). Compared with that in human pancreatic duct epithelial cells (HPDE6-C7), SNHG6 showed the highest expression in PANC-1 cells (1.00 ± 0.06 vs. 3.87 ± 0.13, t = 34.72, P < 0.001) and the lowest expression in human pancreatic cancer cells (MIAPaCa-2) (1.00 ± 0.06 vs. 1.41 ± 0.07, t = 7.70, P = 0.0015). Compared with the levels in the si-negative control group, SNHG6 (0.97 ± 0.05 vs. 0.21 ± 0.06, t = 16.85, P < 0.001), N-cadherin (0.74 ± 0.05 vs. 0.41 ± 0.04, t = 8.93, P < 0.001), Vimentin (0.55 ± 0.04 vs. 0.25 ± 0.03, t = 10.39, P < 0.001), and β-catenin (0.62 ± 0.05 vs. 0.32 ± 0.03, t = 8.91, P < 0.001) were decreased, while E-cadherin (0.65 ± 0.06 vs. 1.36 ± 0.07, t = 13.34, P < 0.001) was increased after SNHG6 knockdown or miR-26a-5p overexpression, accompanied by inhibited cell proliferation, migration, and invasion. SNHG6 overexpression exerted the opposite effects. SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p. Silencing SNHG6 blocked the growth of PC in vivo.ConclusionSilencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p, thus providing further supporting evidence for its use in PC treatment.

Long noncoding RNA SNHG6 contributes to ventricular septal defect formation via negative regulation of miR-101 and activation of Wnt/β-catenin pathway.

This study aimed to investigate the role and regulatory mechanism of small nucleolar RNA host gene 6 (SNHG6), a long noncoding RNA, in the formation of ventricular septal defect (VSD). The expression of SNHG6 in fetal cardiac tissues with VSD, mouse heart embryo development and the differentiation of P19 cells into cardiomyocytes were determined. Moreover, the effect of aberrant expression of SNHG6 on P19 cell proliferation, cell cycle, apoptosis and differentiation was further analyzed to explore the role of SNHG6 in affecting myocardial development. Furthermore, the regulatory mechanism between SNHG6 and miR-101 as well as between SNHG6 and activation of Wnt/β-catenin pathway was investigated. SNHG6 was upregulated in fetal cardiac tissues with VSD, and decreased in the embryonic development of mice and differentiation of P19 cells into cardiomyocytes. Overexpression of SNHG6 inhibited P19 cell proliferation and induced apoptosis, as well as promoted cell differentiation into cardiomyocytes. Furthermore, SNHG6 could negative regulate the expression of miR-101, and the effects of SNHG6 on the modulation of P19 cell function were through negative regulation of miR-101. In addition, overexpression of SNHG6 activated Wnt/β-catenin pathway, which was reversed after overexpression of SNHG6 and miR-101 synchronously. Our study reveals that SNHG6 may contribute to VSD formation via negative regulation of miR-101 and activation of Wnt/β-catenin pathway. SNHG6 may constitute a potential therapeutic target in this disease.

SNHG1 promotes cell proliferation by acting as a sponge of miR-145 in colorectal cancer.

ncRNAs are important regulatory molecules and involve in many physiological cellular processes. Small nucleolar RNA host gene 1 (SNHG1) is a host to 8 snoRNAs and is located in 11q12.3 region of the chromosome. It has been reported to be involved in several cancers. However, the role of SNHG1 in the tumorigenesis of colorectal cancer is still unknown. In this study, SNHG1 was upregulated in colorectal cancers, and SNHG1 expression was correlated with advanced colorectal cancer stage and tumor recurrence. We found that SNHG1 promoted cell proliferation by acting as a sponge of miR-145, a well known tumor suppressor of colorectal cancer. Furthermore, the survival analysis indicated that colorectal cancer patients with higher expression of SNHG1 had a worse prognosis. These findings suggested that SNHG1 may act as a potential therapeutic target for the treatment of colorectal cancer.