Small Nucleolar RNA Host Gene 1 Expression Research Articles

Scoparone inhibits breast cancer cell viability through the NF‑κB signaling pathway.

Scoparone (SCO) is a compound found in the stems and leaves of Artemisia capillaris. The pharmacological uses of SCO include significant hypotensive, cholagogic, anti-inflammatory, analgesic, lipid-lowering, anti-asthmatic and anti-coagulant effects. The present study aimed to verify the anticancer potential of SCO in breast cancer (BC) cells and its underlying molecular mechanism. Cell Counting Kit-8 and flow cytometry were used to analyze the effects of SCO on cell viability and apoptosis. Nucleocytoplasmic separation was used to analyze the location of the long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) in BC cells. Reverse transcription-quantitative PCR was used to analyze the effect of SCO on the expression levels of SNHG12, microRNA (miRNA/miR)-140-3p and tumor necrosis factor receptor associated factor 2 (TRAF2). Western blotting was used to analyze the protein expression levels of TRAF2 and downstream nuclear factor κB (NF-κB) signaling pathways. The results demonstrated that SCO had a time- and dose-dependent inhibitory effect on the viability of BC cells, and that the upregulated lncRNA SNHG12 in BC cells was inhibited by SCO. SNHG12, which was primarily expressed in the cytoplasm, acted as a competing endogenous RNA, sponged miR-140-3p and inhibited the expression of miR-140-3p. The transcriptional activity and translational level of TRAF2, a downstream target of miR-140-3p, decreased following the SCO-mediated suppression of SNHG12 expression. As an upstream effector, TRAF2 activity reduction mediated the inhibition of NF-κB signaling, decreased the viability and migration of BC cells, and promoted BC cell apoptosis. In conclusion, SCO-induced inhibition of viability and promotion of apoptosis in BC cells are achieved through the inhibition of NF-κB signaling, which is associated with regulation of the SNHG12/miR-140-3p/TRAF2 axis. This understanding provides new drug candidates for the treatment of BC and a theoretical basis for biology.

Long noncoding RNA SNHG6 silencing sensitized esophageal cancer cells to 5-FU via EZH2/STAT pathway

Chemotherapy was the main treatment method for esophageal cancer (EC) patients. However, chemotherapy resistance due to multiple factors is a major barrier to EC treatment. For investigating how small nucleolar RNA host gene 6 (SNHG6) affected the 5-fluorouracil (5-FU) resistance in EC as well as its possible molecular mechanism. This work conducted cell viability assay, clone formation, scratch assays together with cell apoptosis for evaluating the roles of SNHG6 and enhancer of zeste homolog 2 (EZH2, the histone-lysine N-methyltransferase). Relevant molecular mechanism was identified by RT-qPCR analysis together with Western-blot (WB) assays. Our data showed that SNHG6 expression increased in EC cells. SNHG6 promotes colony formation and migration, whereas suppresses EC cell apoptosis. SNHG6 silencing markedly promoted 5-FU-mediated suppression on KYSE150 and KYSE450 cells. Additional mechanism studies showed that SNHG6 modulating STAT3 and H3K27me3 via promoting EZH2 level. Similar to the function of SNHG6, abnormal expression of EZH2 promotes the malignancy of EC and intensifies its resistance to 5-FU. In addition, overexpression of EZH2 abolished the role of SNHG6 silencing in 5-FU sensitivity in EC cells. SNHG6 overexpression promoted malignancy of EC and increased EC cell resistance to 5-FU. Besides, further molecular mechanism studies provided a novel regulatory pathways that SNHG6 knockdown promoted EC cell sensitivity to 5-FU by modulating STAT3 and H3K27me3 via promoting EZH2 expression.

LncRNA SNHG1 promotes nasopharyngeal carcinoma development via targeting miR-424-5p.

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck. Distant metastasis and drug resistance are the main causes of cancer-related death. A better understanding of the molecular mechanisms that affect the progression of NPC would contribute to clinical treatment. This paper aims to investigate the effects of the long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) on biological phenotypes of NPC cells and its related mechanisms. The expression of SNHG1 and miR-424-5p in non-cancerous nasopharyngeal mucosa tissues and NPC tissues, as well as in normal nasopharyngeal epithelial cells and NPC cells was detected by qRT-PCR. HK1 and C666-1 cells were transfected with SNHG1 overexpression vector (OE-SNHG1), miR-424-5p mimic, SNHG1 knockdown vector (sh-SNHG1), or miR-424-5p inhibitor, followed by detection of transfection efficiency by qRT-PCR, cell viability by MTT, and invasive and migratory abilities by transwell invasion assay and cell scratch test. Moreover, the relationship between SNHG1 and miR-424-5p was detected by dual-luciferase reporter and RIP assays. In NPC tissues and cells, SNHG1 was upregulated but miR-424-5p was downregulated. Transfection with OE-SNHG1 or miR-424-5p inhibitor promoted proliferative, invasive, and migratory phenotypes of HK1 and C666-1 cells; transfection of sh-SNHG1 or mi-miR-424-5p induced reverse trends. Mechanistically, SNHG1 negatively regulated miR-424-5p expression, and transfection of miR-424-5p inhibitor counteracted the inhibitory effects of sh-SNHG1 on the proliferative, invasive, and migratory phenotypes of HK1 and C666-1 cells. LncRNA SNHG1 promoted proliferation, invasion and migration of NPC cells by repressing miR-424-5p expression.

LncRNA SNHG5 Suppresses Cell Migration and Invasion of Human Lung Adenocarcinoma via Regulation of Epithelial-Mesenchymal Transition.

Long noncoding RNAs (lncRNAs) are gradually being annotated as important regulators of multiple cellular processes. The goal of our study was to investigate the effects of the lncRNA small nucleolar RNA host gene 5 (SNHG5) in lung adenocarcinoma (LAD) and its underlying mechanisms. The findings revealed a substantial drop in SNHG5 expression in LAD tissues, which correlated with clinical-pathological parameters. Transcriptome sequencing analysis demonstrated that the inhibitory effect of SNHG5 was associated with cell adhesion molecules. Moreover, the expression of SNHG5 was shown to be correlated with epithelial-mesenchymal transition (EMT) markers in western blots and immunofluorescence. SNHG5 also had significant effects of antimigration and anti-invasion on LAD cells in vitro. Furthermore, the migration and invasion of A549 cells were suppressed by overexpressed SNHG5 in the EMT progress induced by transforming growth factor β1 (TGF-β1), and this might be due to the inhibition of the expression of EMT-associated transcription factors involving Snail, SLUG, and ZEB1. In LAD tissues, the expression of SNHG5 exhibited a positive association with E-cadherin protein expression but a negative correlation with N-cadherin and vimentin, according to the results of quantitative real-time PCR (qRT-PCR). In summary, the current work demonstrated that the lncRNA SNHG5 might limit cell migration and invasion of LAD cancer via decreasing the EMT process, indicating that SNHG5 might be used as a target for LAD therapeutic methods.

Downregulation of LncRNA SNHG7 Sensitizes Colorectal Cancer Cells to Resist Anlotinib by Regulating miR-181a-5p/GATA6.

Long noncoding RNAs are a novel class of regulators in human cancers. It has been reported that small nucleolar RNA hostgene 7 (SNHG7) can sponge microRNAs to regulate colorectal cancer (CRC) progression. Given its important regulatory role in cancer biology, we wondered whether SNHG7 is involved in drug resistance to anlotinib (ATB) in CRC. To answer this, we quantified the expression of SNHG7 by quantitative real-time PCR. We performed the Cell Counting Kit-8 and Colony formation assay, flow cytometric analysis, RNA pull-down, RNA-binding protein immunoprecipitation assay, and Luciferase reporter assay to confirm the interaction among SNHG7, miR-181a-5p, and GATA6. We found that SNHG7 was significantly upregulated in CRC tissues and cell lines and ATB-resistant cell lines, which was closely related to the poor overall survival of patients. Loss-of-function studies demonstrated that SNHG7 knockdown can inhibit CRC cell proliferation, increase apoptosis, and sensitize CRC cells to resist ATB. Mechanistic studies showed that SNHG7 acted as a competitive endogenous RNA to sponge miR-181a-5p to regulate the expression of GATA6, thereby promoting ATB resistance in ATB-resistant cell lines. In conclusion, SNHG7 plays an important role in ATB resistance, and it may be used to monitor ATB resistance in CRC.

The study of long noncoding RNA SNHG5 and PANDAR genes expression in newly diagnosed egyptian adult acute myeloid leukemia patients

BACKGROUND: Due to their impact on crucial steps in hematopoiesis, long noncoding RNAs (lncRNAs) deregulation potentially accelerates the growth and development of blood cancers like acute myeloid leukemia (AML). The study aimed to look into different expression patterns, prognostic value, and clinical importance of lncRNA small nucleolar RNA host gene 5 (SNHG5) and promoter of cyclin-dependent kinase inhibitor 1A antisense DNA damage-activated RNA (PANDAR) genes in Egyptian adult patients with AML. SUBJECTS AND METHODS: The case–control study was conducted between 2019 and 2022 at the Clinical Pathology Department at the National Cancer Institute, Cairo University, Egypt. The study involved 80 recently diagnosed patients with AML and 20 healthy controls. Real-time quantitative reverse transcription polymerase chain reaction was used to assess the levels of expression of SNHG5 and PANDAR genes. RESULTS: In comparison to healthy controls, there was a significantly higher SNHG5 gene expression (P = 0.026) and PANDAR expression (P < 0.001) in patients’ bone marrow samples. The study of the correlations revealed a significant positive association between SNHG5 and PANDAR genes in AML patients. The overall survival (OS) was significantly better in the low SNHG5 gene expression group than in the high SNHG5 gene expression group. No significant difference was detected regarding the disease-free survival (DFS) between patients with low expression and high expression of the SNHG5 gene. No significant variation between high PANDAR gene and low PANDAR gene expression regarding OS and DFS. CONCLUSION: SNHG5 and PANDAR may have a pathogenic role in AML, and their overexpression might be considered a marker for diagnosis in AML patients in Egypt. SNHG5 expression can be used as a predictor for OS, while PANDAR expression cannot be used as a predictor for OS or DFS in patients.

Long non‑coding RNA SNHG5 promotes osteogenic differentiation of human periodontal ligament stem cells via mediating miR‑23b‑3p/Runx2 axis.

The treatment of bone loss due to periodontitis has posed a great challenge for physicians for decades. Therefore, it is of extraordinary significance to identify an effective regeneration scheme for alveolar bone. This study aimed to investigate long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) whether sponges microRNA-23b-3p (miR-23b-3p) to achieve the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Results revealed that the expression of SNHG5 was upregulated whereas that of miR-23b-3p was downregulated in osteogenic hPDLSCs. Alizarin red staining assays and qRT-PCR demonstrated that SNHG5 silencing or miR-23b-3p overexpression inhibits hPDLSCs osteogenic differentiation and vice versa. In addition, miR-23b-3p partially abolished the promotive effect of SNHG5 on osteogenic differentiation of hPDLSCs. Dual luciferase report and RNA pulldown assay verified that miR-23b-3p is a regulatory target of SNHG5 and that Runx2 is a gene target of miR-23b-3p. In brief, the results demonstrate that SNHG5 promotes the osteogenic differentiation of hPDLSCs by regulating the miR-23b-3p/Runx2 axis. Our study provides novel mechanistic insights into the critical role of lncRNA SNHG5 as a miR-23b-3p sponge to regulate Runx2 expression in hPDLSCs and may serve as a potential therapeutics target for periodontitis.

LncRNA-SNHG1 promotes paclitaxel resistance of gastric cancer cells through modulating the miR-216b-5p-hexokianse 2 axis

Gastric cancer (GC) is one of the most malignant tumors with high incidence and poor prognosis. Currently, the combination of surgery with chemo- or radiotherapy is widely applied therapeutic strategy against GC. However, development of drug resistance severely limited the clinical application of chemotherapy. Small nucleolar RNA host gene 1 (SNHG1) has been reported to be frequently overexpressed in diverse human tumors. Yet, the biological roles and mechanisms of SNHG1 in chemoresistant GC remain unclear. Expressions of lncRNA and miRNA were detected by qRT-PCR. Responses of GC cells to Taxol treatments were evaluated by cell viability assay and apoptosis assay. Glucose metabolism rate was examined by glucose uptake and extracellular acidification rate (ECAR). The lncRNA–miRNA interaction was validated by RNA pull-down assay and luciferase assays. This study reports that expressions of SNHG1 were significantly elevated in patients with GC and gastric cancer cell lines. Silencing SNHG1 effectively suppressed GC cells migration and increased the Taxol sensitivity of GC cells. Moreover, we detected remarkedly upregulated SNHG1 expression and increased glucose metabolism in Taxol resistant cell line, MKN-45 TXR. Low glucose supply rendered Taxol resistant cells more susceptible to Taxol treatment compared with that from MKN-45 parental cells. Bioinformatical analysis, RNA pull-down and luciferase assays verified that SNHG1 functioned as a ceRNA of miR-216b-5p in GC cells. Consistently, we detected miR-216b-5p was significantly downregulated in GC tumor specimens and Taxol resistant GC cells. The hexokinase 2 (HK2), a glucose metabolism key enzyme, was predicted and validated as a direct target of miR-216b-5p in GC cells. Finally, restoration of miR-216b-5p in SNHG1-overexpressing MKN-45 TXR cells successfully overrode the SNHG1-promoted Taxol resistance through targeting the HK2-glycolysis axis. This study uncovered new biological roles and molecular mechanisms of the lncRNA-SNHG1-mediated Taxol resistance of gastric cancer, suggesting targeting the SNHG1-miR-216b-5p-HK2 axis could be a potentially therapeutic approach against chemoresistant gastric cancer.

SNHG3 regulates NEIL3 via transcription factor E2F1 to mediate malignant proliferation of hepatocellular carcinoma.

The involvement of small nucleolar RNA host gene 3 (SNHG3) in cancer regulation has been reported. This study attempted to deeply investigate the molecular regulatory mechanism of SNHG3 on malignant progression of hepatocellular carcinoma (HCC). According to TCGA analysis, high SNHG3 expression was a risk factor for poor prognosis of HCC patients. Therefore, we further detected the mRNA level of SNHG3 in HCC tissue and cells. It was found that SNHG3 was upregulated in HCC tissue and cells. Afterwards, CCK-8 and flow cytometry assays further proved that silencing SNHG3 inhibited HCC cell proliferation while inducing cell apoptosis and G0/G1 phase arrest. It was also attested in vivo experiments that silencing SNHG3 could reduce the volume and weight of tumors and downregulate the Ki-67 expression to suppress HCC tumor growth. Next, it was discovered that SNHG3 increased the binding of E2F1 and NEIL3 promoter region, thereby activating the transcription feature of NEIL3. Lastly, rescue assays indicated that NEIL3 participated in SNHG3-mediated HCC cell cycle, apoptosis and proliferation. All in all, this study revealed the specific regulatory mechanism of SNHG3 in HCC to enable SNHG3 a hopeful marker for HCC diagnosis and treatment.

Polymer nanoparticle delivery of microRNA-1303 suppresses renal cell carcinoma differentiation via regulation of small nucleolar RNA host gene 16

Small nucleolar RNA host gene 16 (SNHG16) participates in some cancers as microRNA (miR)-1303 is also reported to function on proliferation of various cancer cells. This study aimed to assess SNHG16 and miR-1303′s role in renal cell carcinoma (RCC) and its underlying mechanism. RT-qPCR was used to determine SNHG16 and miR-1303 expression in RCC cells (A498, 786-O, ACHN and OS-RC-2) and normal kidney epithelial cells (HK-2). Functional experiment was established to detect the role of miR-1303. After synthesis of nanoparticles carrying miR-1303 and transfection, CCK-8 method and assays were used to evaluate cell growth and apoptosis. The target genes for miR-1303 were predicted using bioinformatics software, and binding of miR-1303 to SNHG16 was evaluated using the dual-luciferase reporter assay. miR-1303 was lowly expressed in RCC cells, with lowest level in A498 (p < 0.05). Overexpressed miR-1303 significantly reduced proliferation ability of RCC cells and induced apoptosis (p < 0.05). Besides, transfection of NP carrying miR-1303 mimic resulted in dramatically decreased migrated cells when reducing the expression of SNHG18 mRNA. The presence of NPs strengthened the inhibitory effect of miR-1303 on RCC. Furthermore, the miR-1303+SNHG16-WT co-transfection group had lower relative luciferase activity compared with miR-1303+SNHG16-MUT co-transfection group (p < 0.05). miR-1303 was down-regulated in RCC and NP delivery of miR-1303 inhibited RCC cell proliferation and differentiation through regulation of SNHG16. These findings suggest miR-1303 may become a potential molecular target for RCC.

LncRNA SNHG16 is Downregulated in Pneumonia and Downregulates miR-210 to Promote LPS-Induced Lung Cell Apoptosis.

Long non-coding RNA Small Nucleolar RNA Host Gene 16 (SNHG16) has been reported to participate in Lipopolysaccharide (LPS)-induced inflammatory pathway, which contributes to pneumonia. This study was therefore conducted to explore the role of SNHG16 in pneumonia. In this study, expression of SNHG16 and microRNA (miR)-210 in pneumonia plasma samples (n = 56) and control samples (n = 60) was detected by RT-qPCR. The potential crosstalk between SNHG16 and miR-210 was analyzed by performing overexpression experiments. MSP was performed to study the role of SNHG16 in methylation of miR-210 gene. Cell apoptosis was analyzed by cell apoptosis assay. Decreased expression levels of SNHG16 and increased expression levels of miR-210 were observed in pneumonia. SNHG16 showed an inverse correlation to miR-210. LPS treatment led to downregulated SNHG16 and upregulated miR-210 in Human Bronchial Epithelial Cells (HBEpCs). In HBEpCs, SNHG16 downregulated miR-210 and increased miR-210 DNA gene methylation. Moreover, SNHG16 suppressed the role of miR-210 in cell apoptosis under LPS treatment. In conclusion, SNHG16 is downregulated in pneumonia, and it downregulates miR-210 possibly through methylation to promote lung cell apoptosis induced by LPS.

Aberrant Circulating SNHG1 Serves as a Biomarker to Distinguish Acute Myocardial Infarction and Construction of a Risk Model for Secondary Heart Failure.

Abstract: Acute myocardial infarction (AMI) is a severe condition observed in patients with coronary heart disease, and heart failure (HF) often occurs after AMI. This study aimed to evaluate the clinical significance of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in the diagnosis and prognosis of AMI and to construct a logistic predict model to determine the risk of post-AMI HF. This study analyzed the data of 229 patients with AMI. Serum SNHG1 levels were examined using quantitative real-time PCR, and its diagnostic value was evaluated using receiver operating characteristic analysis. The predictive value of SNHG1 for HF onset was evaluated using the Kaplan–Meier method and Cox regression analysis. The risk factors and predictive parameters included in the predictive model of post-AMI HF were determined using multivariate logistic regression analysis. In this study, we found that reduced serum SNHG1 was negatively correlated with the Gensini score of patients with AMI. The diagnostic performance of combining cardiac troponin I (cTnI) and creatine kinase (CK)-MB and SNHG1 was the best. Lower SNHG1 expression served as an independent indicator for HF secondary to AMI. A logistic risk model was constructed with the following equation: , and the predictive accuracy of this model was relatively high with an area under the curve of 0.890. Taken together, our results revealed that reduced SNHG1 combining cTnI and CK-MB had the best diagnostic performance in patients with AMI. A logistic risk model based on SNHG1, age, cTnI, CK-MB, left ventricular ejection fraction, and Gensini score may help to determine the development of HF in patients with AMI.

Long noncoding RNA SNHG14 knockdown exerts a neuroprotective role in MPP+-induced Parkinson's disease cell model through mediating miR-135b-5p/KPNA4 axis.

Parkinson's disease (PD) is a neurodegenerative disease resulted from the loss of dopaminergic neurons. Here, we analyzed the role of long noncoding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) in PD using 1-methyl-4-phenyl pyridine (MPP+)-induced PD cell model. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were performed to determine RNA and protein expression, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry (FCM) analysis were conducted to analyze cell viability and apoptosis. Enzyme-Linked Immunosorbent Assay (ELISA) was conducted to analyze the release of inflammatory cytokines. Cytotoxicity was assessed using reactive oxygen species (ROS) assay kit, superoxide dismutase (SOD) activity assay kit and lactate dehydrogenase (LDH) activity assay kit. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the interaction between microRNA-135b-5p (miR-135b-5p) and SNHG14 or karyopherin subunit alpha 4 (KPNA4). MPP+ treatment elevated the expression of SNHG14 in SK-N-SH cells in a dose and time-dependent manner. SNHG14 knockdown alleviated MPP+-induced apoptosis, inflammation, and cytotoxicity in SK-N-SH cells. SNHG14 interacted with miR-135b-5p, and SNHG14 silencing-mediated effects were partly overturned by miR-135b-5p knockdown in PD cell model. Besides, miR-135b-5p interacted with the 3' untranslated region (3'UTR) of KPNA4, and KPNA4 overexpression partly reversed miR-135b-5p overexpression-induced effects in PD cell model. SNHG14 knockdown reduced the protein level of KPNA4 partly by up-regulating miR-135b-5p in SK-N-SH cells. SNHG14 promoted MPP+-induced neuro injury in PD cell model through mediating miR-135b-5p/KPNA4 axis.

Modulation of cisplatin resistance in gastric cancer by LncRNA SNHG15

Background: The role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) in cisplatin-resistance was studied in gastric cancer.
 Methods: The relative SNHG15 expression and its correlation with survival were assayed on the Cancer Genome Atlas data and confirmed with the clinical samples we collected. Cisplatin-resistant MKN45 cell line (MKN45 CR) was established. SNHG15 plasmid and SNHG15 shRNA plasmid were transfected into MKN45 cells and MKN45 CR cells. Colony formation analysis and cell counting kit-8 assay were utilized to determine cell proliferation and viability. The binding between SNHG15 and zeste 2 polycomb repressive complex 2 subunit (EZH2) was testified with RNA immunoprecipitation (RIP). The promoter activity of phosphatase and tensin homolog (PTEN) was evaluated by luciferase reporter assay.
 Results: High SNHG15 expression was correlated with the poor overall survival of gastric cancer patients, and cisplatin treatment can induce time and dose-dependent up-regulation of SNHG15. At the same time, SNHG15 overexpression could promote the cisplatin resistance, while SNHG15 inhibition could diminish the cisplatin resistance. RIP assays confirmed the interaction of SNHG15 with EZH2. More importantly, SNHG15 inhibited PTEN promoter activity by reducing EZH2 recruitment in MKN45 CR cells.
 Conclusion: SNHG15 epigenetically prohibits PTEN expression by recruiting EZH2 in gastric cancer cisplatin-resistant cells.

Long non‐coding RNA SNHG5 mediates periodontal inflammation through the NF‐κB signalling pathway

We investigated the role of long non-coding RNAs and small nucleolar RNA host gene 5 (SNHG5) in the pathogenesis of periodontitis. A ligature-induced periodontitis mouse model was established, and gingival tissues were collected from patients with periodontitis and healthy controls. Inflammatory cytokines were detected using quantitative reverse transcription-polymerase chain reaction and western blotting analyses. Direct interactions between SNHG5 and p65 were detected by RNA pull-down and RNA immunoprecipitation assays. Micro-computed tomography, haematoxylin and eosin staining, and immunohistochemical staining were used to measure periodontal bone loss. SNHG5 expression was down-regulated in human and mouse periodontal tissues compared to that in the healthy controls. In vitro experiments demonstrated that SNHG5 significantly ameliorated tumour necrosis factor α-induced inflammation. Mechanistically, SNHG5 directly binds to the nuclear factor-kappa B (NF-κB) p65 subunit and inhibits its translocation, thereby suppressing the NF-κB signalling pathway activation and reducing the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing three inflammasome expression. Locally injecting si-SNHG5 aggravated the periodontal destruction. This study revealed that SNHG5 mediates periodontal inflammation through the NF-κB signalling pathway, providing a potential therapeutic target for periodontitis treatment.

Long non-coding RNA SNHG3 promotes prostate cancer progression by sponging microRNA-1827.

Long non-coding RNAs (lncRNAs) are important biological factors that contribute to the initiation and progression of different types of cancer, including gastric, bladder and colorectal cancer. Small nucleolar RNA host gene 3 (SNHG3) has been implicated in prostate cancer (PCa) progression. However, the expression pattern and function of SNHG3 in PCa remain unclear, impeding the development of novel treatment strategies for this cancer. The present study aimed to investigate a combination of molecular and biochemical approaches to determine the role of SNHG3 in patients at different stages of disease, and elucidate the pathway by which SNHG3 affects PCa progression. A Cell Counting Kit-8 assay was used to assess cell proliferation. Transwell assays were used to analyze cell migration and invasion. Reverse transcription-quantitative PCR and western blotting were used to evaluate the expression levels of RNAs and proteins, respectively. The results demonstrated that SNHG3 expression was upregulated in PCa tissues downloaded from The Cancer Genome Atlas database, which was associated with poor prognosis. Furthermore, cell proliferation, migration and invasion were significantly inhibited following SNHG3 knockdown in vitro, the effects of which were reversed following overexpression of SNHG3 in PCa cells. Bioinformatic analysis revealed that microRNA (miRNA/miR)-1827 was a downstream target of SNHG3. The direct interaction between SNHG3 and miR-1827 was validated via the dual-luciferase reporter and RNA immunoprecipitation assays. Pearson's correlation analysis demonstrated that SNHG3 expression was negatively correlated with miR-1827 expression at different stages of PCa. Furthermore, rescue assays indicated that cotransfection with small interfering-SNHG3 and miR-1827 inhibitor reversed the effects of SNHG3 knockdown on cell proliferation, migration and invasion. In addition, SNHG3 knockdown in vivo suppressed tumor growth. Notably, lncRNA SNHG3 promoted PCa progression through miR-1827 via the Wnt/AKT/mTOR pathway. Taken together, the results of the present study suggest that SNHG3 promotes PCa progression by sponging miR-1827, indicating that SNHG3 may be a promising diagnostic and therapeutic target of PCa.

LncRNA SNHG15 as a ceRNA modulates Osteoclast Differentiation, Proliferation, and Metastasis by Sponging miR-381-3p/NEK2 Axis.

Background A growing number of studies have shown that long noncoding RNAs play an important role in osteoclast differentiation. However, there are few studies on the roles of lncRNA small nucleolar RNA host gene 15 (SNHG15) in osteoclast differentiation. Methods The expressions of SNHG15, miR-381-3p, and never in mitosis-related kinase 2 (NEK2) mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR); Western blot detected NEK2 and osteoclast markers (Cathepsin K, CTSK), matrix metalloproteinase 9 (MMP9), nuclear factor of activated T cell 2 (NFAT2), and tartrate-resistant acid phosphatase (TRAP) protein levels; cell proliferation was detected by Cell Counting Kit-8 (CCK-8), and the formation of osteoclasts was observed by TRAP staining; the F-actin skeleton was stained with tetramethylrhodamine isothiocyanate (TRITC) phalloidin; cell migration rate was detected by Transwell; dual-luciferase reporter gene assay and RNA-binding protein immunoprecipitation (RIP) assay verified the targeting relationship between miR-381-3p, SNHG15, and NEK2. Results The expression of SNHG15 was increased in THP-1 cells stimulated by macrophage colony-stimulating factor (M-CSF)/receptor activator of nuclear factor-kappa B ligand (RANKL). Overexpression of SNHG15 significantly promoted the proliferation, migration, osteoclast differentiation, and expression of osteoclast markers CTSK, MMP9, NFAT2, and TRAP of THP-1 cells induced by M-CSF/RANKL. Knockdown of SNHG15 reversed this effect. Overexpression of SNHG15 downregulated the inhibitory effect of overexpression of miR-381-3p on the proliferation, migration, and differentiation of THP-1 cells induced by M-CSF/RANKL. Knockdown of miR-381-3p reversed the inhibitory effect of knockdown of NEK2 on the proliferation, migration, and differentiation of THP-1 cells induced by M-CSF/RANKL. Conclusion SNHG15 acted as a ceRNA promoted the proliferation, migration, and differentiation of THP-1 cells induced by M-CSF/RANKL through sponging miR-381-3p to promote the expression of NEK2.

LncRNA SNHG1 promotes sepsis-induced myocardial injury by inhibiting Bcl-2 expression via DNMT1.

Myocardial injury is a frequently occurring complication of sepsis. This study aims to investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1)‐mediated DNA methyltransferase 1/B‐cell lymphoma‐2 (DNMT1/Bcl‐2) axis in sepsis‐induced myocardial injury. Mice and HL‐1 cells were treated with lipopolysaccharide (LPS) to establish animal and cellular models simulating sepsis and inflammation. LncRNA SNHG1 was screened out as a differentially expressed lncRNA in sepsis samples through microarray profiling, and the upregulated expression of lncRNA SNHG1 was confirmed in myocardial tissues of LPS‐induced septic mice and HL‐1 cells. Further experiments suggested that silencing of lncRNA SNHG1 reduced the inflammation and apoptotic rate of LPS‐induced HL‐1 cells. LncRNA SNHG1 inhibited Bcl‐2 expression by recruiting DNMT1 to Bcl‐2 promoter region to cause methylation. Inhibition of Bcl‐2 promoter methylation reduced the inflammation and apoptotic rate of LPS‐induced HL‐1 cells. In vivo experiments substantiated that lncRNA SNHG1 silencing alleviated sepsis‐induced myocardial injury in mice. Taken together, lncRNA SNHG1 promotes LPS‐induced myocardial injury in septic mice by downregulating Bcl‐2 through DNMT1‐mediated Bcl‐2 methylation.

Identifying a novel KLF2/lncRNA SNHG12/miR-494-3p/RAD23B axis in Spare Nerve Injury-induced neuropathic pain

Spinal cord injury (SCI) is a devastating condition for patients, affecting nearly 2.5 million people globally. Multiple side effects of SCI have resulted in a terrible life experience for SCI patients, of which neuropathic pain has attracted the most scientific interest. Even though many efforts have been made to attenuate or eliminate neuropathic pain induced by SCI, the outcomes for patients are still poor. Therefore, identifying novel diagnosis or therapeutic targets of SCI-induced neuropathic pain is urgently needed. Recently, multiple functions of long non-coding RNA (lncRNA) have been elucidated, including those in SCI-induced neuropathic pain. In this study, lncRNA small nucleolar RNA host gene 12 (SNHG12) was found to be upregulated in the dorsal root ganglion (DRGs) of rats with spare nerve injury (SNI). By constructing SCI rat models, we found that lncRNA SNHG12 expression was increased in the DRGs, and mainly distributed in the cytoplasm of PC12 cells. Paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and enzyme linked immunosorbent assay (ELISA) results indicated that lncRNA SNHG12 knockdown attenuated SNI-induced neuropathic pain, and decreased the expression levels of interleukin (IL)−1β, IL-6, and tumour necrosis factor α (TNF-α) in the DRGs. Bioinformatics analysis, RNA pull-down, chromatin immunoprecipitation (ChIP), and luciferase reporter gene assays showed that lncRNA SNHG12 regulates the RAD23 homologue B, nucleotide excision repair protein (RAD23B) expression, through targeting micro RNA (miR)−494-3p. Furthermore, the study indicated that Kruppel-Like Factor 2 (KLF2) could regulate lncRNA SNHG12 expression in PC12 cells. This study identified a novel KLF2/lncRNA SNHG12/miR-494-3p/RAD23B axis in SNI-induced neuropathic pain, which might provide a new insight for developing novel diagnosis, or therapeutic targets of SCI-induced neuropathic pain in the future.

Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression.

Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.