Non-coding RNA Small Nucleolar RNA Host Gene 1 Research Articles

Long noncoding RNA SNHG1 promotes breast cancer progression by regulating the miR-641/RRS1 axis

An increasing number of studies have indicated the crucial involvement of long non-coding RNAs (lncRNAs) in the onset and progression of malignancies. However, a complete understanding of the molecular mechanism underlying the effect of abnormally expressed lncRNAs on breast cancer (BC) remains elusive. This study aimed to elucidate the influence of the lncRNA small nucleolar RNA host gene 1 (SNHG1) on BC progression and its underlying mechanism. Our findings revealed a conspicuous up-regulation of SNHG1 in both BC tissues and cells. The downregulation of SNHG1 was observed to inhibit BC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) processes, while simultaneously promoting apoptosis. Furthermore, dual-luciferase reporter gene and RNA pull-down assays established that SNHG1 targeted miR-641 expression, while miR-641 targeted RRS1. Rescue studies demonstrated that in vitro SNHG1 silencing could be reversed by the miR-641 inhibitor, as well as by RRS1 upregulation. Moreover, in vivo downregulation of SNHG1 was found to inhibit BC growth. Through the inhibition of the miR-641 level, SNHG1 elevated the level of the downstream target RRS1, thereby fostering BC growth, migration, and invasion while inhibiting apoptosis. These findings suggest that SNHG1 may represent a potential therapeutic target for BC treatment.

Suppression of long noncoding RNA SNHG6 alleviates cigarette smoke-induced lung inflammation by modulating NF-κB signaling.

Chronic obstructive pulmonary disease (COPD) is a widespread inflammatory disease with a high mortality rate. Long noncoding RNAs play important roles in pulmonary diseases and are potential targets for inflammation intervention. The expression of small nucleolar RNA host gene 6 (SNHG6) in mouse lung epithelial cell line MLE12 with or without cigarette smoke extract (CSE) treatment was first detected using quantitative reverse-transcription PCR. ELISA was used to evaluate the release of inflammatory cytokines (TNF-α, IL-1β, and IL-6). The binding site of miR-182-5p with SNHG6 was predicted by using miRanda, which was verified by double luciferase reporter assay. Here, we revealed that SNHG6 was upregulated in CS-exposed MLE12 alveolar epithelial cells and lungs from COPD-model mice. SNHG6 silencing weakened CS-induced inflammation in MLE12 cells and mouse lungs. Mechanistic investigations revealed that SNHG6 could upregulate IκBα kinase through sponging the microRNA miR-182-5p, followed by activated NF-κB signaling. The suppressive effects of SNHG6 silencing on CS-induced inflammation were blocked by an miR-182-5p inhibitor. Overall, our findings suggested that SNHG6 regulates CS-induced inflammation in COPD by activating NF-κB signaling, thereby offering a novel potential target for COPD treatment.

Long noncoding RNA SNHG6 promotes the malignant phenotypes of ovarian cancer cells via miR-543/YAP1 pathway

The long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) acts as an oncogene in several cancers, and is highly expressed in ovarian cancer. MiR-543, a tumor suppressor, was expressed lowly in ovarian cancer. However, whether SNHG6 performed its oncogenic role via miR-543 in ovarian cancer, as well as the underlying mechanism is still not clear. In this study, we showed that the levels of SNHG6 and Yes-associated protein 1 (YAP1) were significantly elevated, while the level of miR-543 was significantly decreased, in ovarian cancer tissues compared with adjacent normal samples. We demonstrated that overexpression of SNHG6 significantly promoted the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of ovarian cancer cells SKOV3 and A2780. Knockdown of SNHG6 showed the opposite effects. MiR-543 level was negatively correlated with the SNHG6 level in ovarian cancer tissues. SHNG6 overexpression significantly inhibited the expression of miR-543, and SHNG6 knockdown significantly elevated the expression of miR-543 in ovarian cancer cells. The effects of SNHG6 on ovarian cancer cells were abrogated by miR-543 mimic, and strengthened by anti-miR-543. YAP1 was identified as a target of miR-543. Forced expression of miR-543 significantly inhibited the expression of YAP1. Moreover, YAP1 overexpression could reverse the effects of SNHG6 downregulation on the malignant phenotypes of ovarian cancer cells. In summary, our study showed that SNHG6 promoted the malignant phenotypes of ovarian cancer cells via miR-543/YAP1 pathway.

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.

Long non-coding RNA SNHG16 silencing inhibits proliferation and inflammation in Mycobacterium tuberculosis-infected macrophages by targeting miR-140-5p expression.

The study investigated the clinical diagnostic value of long non-coding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) and explored its underlying molecular mechanism through Mycobacterium tuberculosis (M. tuberculosiinfection of macrophages. RT-qPCR analysis of the serum SNHG16 levels of the 66 healthy individuals, 67 latent TB (LTB) patients, and 67 active TB (ATB) patients. The receiver-operating characteristic (ROC) curve to detect the clinical diagnostic value of SNHG16 in TB patients. In vitro, M. tuberculosis-infected macrophages, CCK-8 and ELISA to detect cell proliferation and inflammatory factor levels. Luciferase reported assay was performed to analyze the targeting relationship between SNHG16 and miR-140-5p. SNHG16 was significantly elevated in TB patients, and among them, ATB patients were higher than LTB patients. ROC confirmed that SNHG16 could distinguish LTB patients from healthy controls, and ATB patients from LTB patients, and can be used as a good diagnostic biomarker for TB. M. tuberculosis infection increased SNHG16 levels and promoted the proliferation and inflammation in macrophages. However, SNHG16 silencing significantly reversed the effect of infection. miR-140-5p, a direct target miRNA of SNHG16, was down-regulated in TB patients and was negatively correlated with SNHG16. When miR-140-5p was inhibited, the alleviating effect of SNHG16 silencing on M. tuberculosis infection proliferation and inflammation was significantly reversed. The present results suggested that SNHG16 may be a new diagnostic biomarker for TB patients and SNHG16 silencing may alleviate TB by inhibiting the proliferation of macrophages in TB by regulation miR-140-5p.

Long non-coding RNA SNHG1 promotes bladder cancer progression by upregulating EZH2 and repressing KLF2 transcription

ObjectiveLong Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression. MethodThe expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established. ResultsSNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription. ConclusionOur study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.

Long Noncoding RNA SNHG1 Regulates LMNB2 Expression by Sponging miR-326 and Promotes Cancer Growth in Hepatocellular Carcinoma.

ObjectiveThe purpose of the study is to explore the potential competing endogenous RNA (ceRNA) network and investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in hepatocellular carcinoma (HCC) development.MethodsBy analyzing the data of HCC in The Cancer Genome Atlas (TCGA) database, we included differentially expressed lncRNA and microRNA (miRNA) profiles and constructed ceRNA networks related to the prognosis of HCC patients. qRT-PCR, Western blotting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell assay, and the nude mouse model were employed to test the effects of SNHG1 and LMNB2 on tumor proliferation and growth in vitro and in vivo.ResultsIn the study, we identified 115 messenger RNAs (mRNAs), 12 lncRNAs, and 37 miRNAs by intersecting differentially expressed genes (DEGs) in TCGA and StarBase databases. Then, SNHG1–miR-326–LMNB2 pathway came into notice after further survival analysis and hub gene screening. Our results showed that SNHG1 expression was upregulated significantly in HCC tissues and cell lines. Downregulation of both LMNB2, the target of miR-326 in HCC, and SNHG1 inhibited tumor proliferation and growth in vitro and in vivo. Furthermore, SNHG1 could regulate LMNB2 expression through binding to miR-326 in HCC cell lines.Conclusion SNHG1 is a promising prognostic factor in HCC, and the SNHG1–miR-326–LMNB2 axis may be a potential therapeutic target for HCC.

The Long Non-coding RNA SNHG12 Functions as a Competing Endogenous RNA to Modulate the Progression of Cerebral Ischemia/Reperfusion Injury.

Increasing research has proved that long non-coding RNAs (lncRNAs) play a critical role in a variety of biological processes. However, their functions in cerebral ischemia are still unclear. We found that the small nucleolar RNA host gene 12 (SNHG12) is a new type of lncRNA induced by ischemia/reperfusion. Here, we show that the expression of SNHG12 was upregulated in the brain tissue of mice exposed to middle cerebral artery occlusion/reperfusion (MCAO/R) and primary mouse cerebral cortex neurons treated with oxygen-glucose deprivation/reoxygenation (OGD/R). Mechanistically, SNHG12 knockdown resulted in larger infarct sizes and worse neurological scores in MCAO/R mice. Consistent with the in vivo results, SNHG12 upregulation significantly increased the viability and prevented apoptosis of neurons cultured under OGD/R conditions. In addition, we found that SNHG12 acts as a competing endogenous RNA (ceRNA) with microRNA (miR)-136-5p, thereby regulating the inhibition of its endogenous target Bcl-2. Moreover, SNHG12 was proven to target miR-136-5p, increasing Bcl-2 expression, which finally led to the activation of PI3K/AKT signaling. In conclusion, we demonstrated that SNHG12 acts as a ceRNA of miR-136-5p, thereby targets and regulates the expression of Bcl-2, which attenuates cerebral ischemia/reperfusion injury via activation of the PI3K/AKT pathway. This knowledge helps to better understand the pathophysiology of cerebral ischemic stroke and may provide new treatment options for this disease.

Long noncoding RNA SNHG6 promotes oesophageal squamous cell carcinoma by downregulating the miR-101-3p/EZH2 pathway.

Long noncoding RNAs (LncRNAs) have been reported to play a vital role in the development of oesophageal squamous cell carcinoma (OSCC). Our previous study revealed that the significant upregulation of the LncRNA small nucleolar RNA host gene 6 (SNHG6) in OSCC promotes OSCC tumourigenesis. However, the mechanisms underlying the dynamics of SNHG6 expression in OSCC have rarely been studied. In this study, we verified the tumour-promoting effect of SNHG6 through sponging miR-101-3p, and their levels were negatively correlated in human samples of OSCC. In addition, miR-101-3p overexpression reversed the effect of SNHG6. Moreover, we confirmed that SNHG6/miR-101-3p affects OSCC by regulating the expression of the enhancer of zeste 2 (EZH2). The effect of EZH2 silencing resembled closely that of SNHG6 knockdown. EZH2 silencing inhibited the expression of protein cyclin D1 and β-catenin, but in contrast, it enhanced the expression of E-cadherin. These findings demonstrated the oncogenic role of SNHG6, which promotes OSCC progression by regulating the expression of EZH2 through its interaction with miR-101-3p. These findings may help in improving the diagnosis and treatment methods of OSCC.

Long noncoding RNA SNHG6 promotes papillary thyroid cancer cells proliferation via regulating miR-186/CDK6 axis

Papillary thyroid cancer (PTC) is a common endocrine malignancy, and its incidence rate has been increasing in recent years. Long noncoding RNAs (lncRNAs) participate in cell biological processes through a variety of regulatory ways, and play an essential role in tumor development. This study explored the expression of lncRNA small nucleolar RNA host gene 6 (SNHG6) in PTC by bioinformatics analysis, and quantitative real-time PCR (qRT-PCR). Cell counting kit-8 (CCK-8) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to study the effect of SNHG6 on the proliferation of PTC cells. Luciferase reporter gene assay and western blot were used to study the mechanism. SNHG6 was highly expressed in PTC tissue samples and cell lines. In vitro, overexpression of SNHG6 promoted the proliferation of PTC cells, while silencing SNHG6 inhibited the proliferation of PTC cells. miR-186 is the downstream target of SNHG6. SNHG6 regulates the proliferation of PTC cells through miR-186. In addition, CDK6 is the target gene of miR-186, which can inhibit the expression of CDK6 protein. SNHG6 can promote the expression of CDK6 by regulating miR-186. SNHG6 is highly expressed in PTC and can promote the proliferation of PTC cells by regulating the miR-186/CDK6 axis, which is expected to become a potential therapeutic target for PTC.

Long non-coding RNA SNHG16 as a potential biomarker in hepatocellular carcinoma: A meta-analysis.

Small nucleolar RNA host gene 16 (SNHG16) has recently been reported as a potential biomarker in various cancers. However, the prognostic value of SNHG16 in hepatocellular carcinoma (HCC) has not been investigated yet. Therefore, the purpose of this study was to reveal the association between SNHG16 expression and clinicopathological characteristics of HCC.Standards-compliant literature was retrieved from multiple public databases, and data on overall survival, disease-free survival, and clinicopathological characteristics related to SNGH16 were extracted and meta-analysis was performed. Additionally, the Cancer Genome Atlas data were analyzed through the gene expression profiling interactive analysis database to verify previous results.A total of 5 reports involving 410 patients with HCC were enrolled. The high expression of SNHG16 indicated worse overall survival (hazard ratio, 2.10; 95% CI, 1.22–3.60; P = .007) and disease-free survival (hazard ratio, 3.38; 95% CI, 1.10–10.40; P = .03). Additionally, the high expression of SNHG16 predicted a larger tumor size, metastasis, and advanced TNM stage.SNHG16 could serve as a potential biomarker of poor prognosis in HCC.

RETRACTED ARTICLE: Long noncoding RNA SNHG1 promotes TERT expression by sponging miR-18b-5p in breast cancer

BackgroundLong noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a positive role in the progression of human malignant tumors. However, the molecular mechanism of SNHG1 remains elusive in breast cancer.ResultsLncRNA SNHG1 was upregulated and had a positive relationship with poor prognosis according to bioinformatics analysis in pan-cancer including breast cancer. Silencing SNHG1 inhibited tumorigenesis in breast cancer both in vitro and in vivo. Mechanistically, SNHG1 functioned as a competing endogenous RNA (ceRNA) to promote TERT expression by sponging miR-18b-5p in breast cancer. miR-18b-5p acted as a tumor repressor in breast cancer. Moreover, the combination of SNHG1 knockdown and TERT inhibitor administration showed a synergistic inhibitory effect on breast cancer growth in vivo. Finally, E2F1 as a transcription factor, binding to SNHG1 promoter and enhanced SNHG1 transcription in breast cancer.ConclusionsOur results provide a comprehensive understanding of the oncogenic mechanism of lncRNA SNHG1 in breast cancer. Importantly, we identified a novel E2F1–SNHG1–miR-18b-5p–TERT axis, which may be a potential therapeutic target for breast cancer. Our results also provided a potential treatment for breast cancer when knockdown SNHG1 and TERT inhibitor administration simultaneously.

Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells.

Background: Small nucleolar RNA host gene 12 (SNHG12) is a newly identified long non-coding RNA (lncRNA) whose involvements have been explored in several cancers. Our study aimed to explore the functions of SNHG12 on intrahepatic cholangiocarcinoma (ICC) progression and its interaction with miR-199a-5p and Klotho.Methods: RT-PCR was performed to examine the expressions of SNHG12, miR-199a-5p and Klotho in ICC cells. Cell counting kit-8 (CCK-8), colony formation assays and transwell assays were applied to analyze the proliferation, migration and invasion of ICC cells. Luciferase assays, RIP assays and RNA pull-down assays were carried out to demonstrate the direct binding relationships among SNHG12, miR-199a-5p and Klotho. The xenograft nude models were applied to test the effects of SNHG12 on ICC tumor growth.Results: The expression of SNHG12 and Klotho was distinctly increased in ICC cells, while miR-199a-5p expressions were decreased. Functionally, the silence of SNHG12 inhibited the proliferation and metastasis of ICC cells, while miR-199a-5p overexpression exhibited an opposite result. Mechanistically, Knockdown of SNHG12 significantly suppressed the expressions of miR-199a-5p by sponging it, and then increased Klotho expression. The final in vivo experiments suggested that the silence of SNHG12 distinctly inhibited tumor growth.Conclusion: Our findings indicated that SNHG12 inhibited cell proliferation and metastasis process of ICC cells through modulating the miR-199a-5p/Klotho axis and it is expected to become a potential therapeutic target for ICC.

Long non-coding RNA SNHG1 stimulates ovarian cancer progression by modulating expression of miR-454 and ZEB1.

Ovarian cancer (OC) is highly prevalent and is associated with high mortality rates due to metastasis and relapse. In this study, we assessed the role of long non‐coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in OC to gain further insight into mechanisms that contribute to its aggressiveness. We analyzed the correlation between SNHG1, miR‐454 and zinc finger E‐box‐binding homeobox 1 (ZEB1) using a dual‐luciferase reporter assay. Alterations in cell metastasis and invasiveness were observed using wound‐healing and Transwell invasion assays, respectively. Tumor xenografts allowed us to monitor liver metastasis of mice injected with A2780 cells. We found that SNHG1 is overexpressed in OC. Downregulation of SNHG1 promoted miR‐454 expression and reduced ZEB1 levels. In addition, knockdown of SNHG1, also reduced the aggressiveness of A2780 and SK‐OV3 cells. Furthermore, SNHG1 downregulation by siRNA hindered cell migration and invasion; however, this effect was reversed by co‐transfection of miR‐454 into A2780 and SK‐OV3 cells. Moreover, SNHG1 increased ZEB1 expression by downregulating miR‐454 and activated Akt signaling, thereby promoting epithelial‐mesenchymal transition and enhancing the invasiveness of OC cells. Tumor xenograft analyses confirmed that SNHG1 affects OC proliferation and metastasis in vivo. In summary, our data demonstrate that SNHG1 plays crucial roles in tumor progression and may be a useful maker for OC prognosis.

Long noncoding RNA SNHG1 protects brain microvascular endothelial cells against oxygen-glucose deprivation/reoxygenation-induced injury by sponging miR-298 and upregulating SIK1 expression.

Growing evidence shows that long non-coding RNAs (lncRNAs) are widely involved in the progression of multiple diseases, including ischemic stroke. The aim of this study was to explore the function and underlying mechanism of lncRNAs small nucleolar RNA host gene 1 (SNHG1) in ischemic stroke. SNHG1 and salt-induced kinase 1 (SIK1) were upregulated in oxygen-glucose deprivation/reperfusion (OGD/R)-induced bEnd3 cells. SNHG1 downregulation promoted OGD/R-induced injury through decreasing cell proliferation and increasing apoptosis, which was reversed by upregulating SIK1 or downregulating miR-298. Moreover, SIK1 interference had similar functions with SNHG1 knockdown in OGD/R-treated bEnd3 cells. In addition, miR-298 was a direct target of SNHG1 and could specifically bind to SIK1. Furthermore, SNHG1 functioned as a molecular sponge of miR-298 to regulate SIK1 expression. SNHG1 knockdown enhanced OGD/R-induced injury in bEnd3 cells by regulating miR-298/SIK1 axis, which might provide promising therapeutic target for treatment of ischemic stroke.

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.

YY1-modulated long non-coding RNA SNHG12 promotes gastric cancer metastasis by activating the miR-218-5p/YWHAZ axis.

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) plays important roles in the pathogenesis and progression of cancers. However, the role of SNHG12 in the metastasis of gastric cancer (GC) has not yet been thoroughly investigated. In the present study, we demonstrated that SNHG12 was upregulated in GC tissues and cell lines. In addition, the expression level of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM stage and lymph node metastasis and was associated with disease-free survival (DFS) and overall survival (OS) in GC patients. In vivo and in vitro assays indicated that SNHG12 promotes GC metastasis and epithelial-mesenchymal transition (EMT). Bioinformatics and mechanistic analyses revealed that SNHG12 can directly target miR-218-5p to regulate YWHAZ mRNA, forming an SNHG12/miR-218-5p/YWHAZ axis and decreasing the ubiquitination of β-catenin. In addition, SNHG12 stabilizes CTNNB1 mRNA by binding with HuR, thus activating the β-catenin signaling pathway. Further analysis also revealed that the transcription factor YY1 negatively modulates SNHG12 transcription. In conclusion, SNHG12 is a potential prognostic marker and therapeutic target for GC. Negatively modulated by YY1, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and stabilizing CTNNB1 via activation of the β-catenin signaling pathway.

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.

Long Noncoding RNA SNHG12 Promotes Prostate Tumor Occurrence and Progression via AKT Regulation.

The small nucleolar RNA host gene 12 (SNHG12) has been reported to play an important role in the tumorigenesis and progression of PCa, but the functional underlying mechanism has not been studied clearly. We detected the expression level of SNHG12 in PCa tissues and matched adjacent normal tissues that were collected from 85 patients. Then, colony formation assays, MTT experiments, and flow cytometry were used to examine the effect of SNHG12 on proliferation, cell cycle distribution, and apoptosis of DU145 cells. Further, Transwell invasion assay was utilized to assess whether SNHG12 participates in PCa cell invasion and affects the secretion of VEGF secretion in DU145 cells. Finally, we investigated the effect of SNHG12 on tumor growth in vivo. We found that SNHG12 promoted cell proliferation and suppressed apoptosis in PCa cells, which suggests that SNHG12 is probably a novel PCa biomarker and therapy target of PCa.

Long non-coding RNA SNHG1 regulates rheumatoid synovial invasion and proliferation by interaction with PTBP1

Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) present proliferative and aggressive cell phenotype. RA-FLSs are the essential effector cells that lead to symptoms like synovial inflammation and joint destruction. Currently, the cause of RA-FLSs involving in the pathological process of RA remains unknown. Accumulate researches have demonstrated that lncRNAs may play a critical role in regulating the biological behaviors of RA-FLSs, but the mechanism is still unclear. Here, we found that lncRNA small nucleolar RNA host gene 1 (SNHG1) is up-regulated in RA-FLSs compared with FLSs from trauma arthritis and osteoarthritis patients. The results suggest that SNHG1 in RA-FLSs helps to sustain the cellular functions of proliferation, migration and invasion. Furthermore, the regulation mechanism depends on the interaction between SNHG1 and polypyridine tract-binding protein 1 (PTBP1). This interaction influences PTBP1 expression that participates in the regulation of RA-FLSs biological behaviors. Our results suggest that up-regulated SNHG1 of RA-FLSs may contribute to synovial aggression and disease progression in RA and be favourable for RA treatment target RA-FLSs.