Non-coding RNA SNHG1 Research Articles

Long noncoding RNA SNHG7 accelerates prostate cancer proliferation and cycle progression through cyclin D1 by sponging miR-503

Increasing evidence has indicated the important roles of long non-coding RNAs (lncRNAs) in tumorigenesis and cellular progression, including prostate cancer. In this study, we aim to investigate the expression level of SNHG7 and its biological functions on prostate cancer cells. Results indicated that SNHG7 expression was significantly up-regulated in prostate cancer tissue and cell lines. Besides, the overexpression of SNHG7 was closely correlated with the poor prognosis. In vitro and in vivo, experiments demonstrated that SNHG7 knockdown markedly inhibited prostate cancer proliferation and cycle-related protein (CDK4, CDK6, Cyclin D1), induced cell cycle arrest at G0/G1 phase and suppressed tumor growth. Moreover, miR-503 was predicted by bioinformatics tools and validated using luciferase reporter assay to both directly inhibited SNHG7 and Cyclin D1 expression by targeting their RNA 3′-UTR. In conclusion, results present that SNHG7 regulates the cycle progression and acts as an oncogenic gene in the prostate cancer tumorigenesis via miR-503/Cyclin D1 pathway, revealing the vital role of lncRNA/miRNA/mRNA axis in prostate cancer carcinogenesis.

The long noncoding RNA SNHG1 promotes nucleus pulposus cell proliferation through regulating miR-326 and CCND1

Aberrant nucleus pulposus cell proliferation is implicated in the development of intervertebral disk degeneration (IDD). Recent studies have suggested that long noncoding RNAs (lncRNAs) can modulate cell proliferation in several pathological conditions. Here, we indicate that expression of SNHG1 was upregulated in IDD tissues compared with control tissues and that higher SNHG1 expression was associated with disk degeneration grade. In addition, we show that ectopic expression of SNHG1 promoted nucleus pulposus (NP) cell proliferation and increased the PCNA and cyclin D1 expression in NP cells. Ectopic expression of SNHG1 inhibited miR-326 expression in nucleus pulposus cells and promoted CCND1 expression, which is a direct target gene of SNHG1. Moreover, we demonstrate that expression of miR-326 was downregulated in IDD tissues compared with control tissues and that lower SNHG1 expression was associated with disk degeneration grade. Expression of miR-326 was negatively associated with SNHG1 expression in disk degeneration tissues. Overexpression of miR-326 inhibited NP cell growth and inhibited PCNA and cyclin D1 expression in NP cells. Furthermore, we show that overexpression of SNHG1 promoted nucleus pulposus cell proliferation through inhibiting miR-326 expression. These data shed novel light on the role of SNHG1 in the pathogenesis of IDD.

Long non-coding RNA SNHG16 promotes cell growth and metastasis in ovarian cancer.

To investigate the expression of long non-coding RNA SNHG16 in ovarian cancer and to further investigate its role in the development of ovarian cancer as well as its potential regulatory mechanism. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of SNHG16 in 103 ovarian cancer tissues and normal tissues; the relationship between the expression of SNHG16 and the pathological parameters of ovarian cancer and the prognosis of patients was also analyzed. qRT-PCR was used to further verify the expression of SNHG16 in the ovarian cancer cells. After establishment of SNHG16 knockdown expression model in ovarian cancer cells SKOV-3 and HO8910 using small interfering RNA, the effect of SNHG16 on biological function of ovarian cancer cells was analyzed via cell counting kit-8 (CCK8), transwell invasion and migration assay. Finally, its potential mechanism was analyzed by Western Blot. qRT-PCR results showed that the expression of SNHG16 in ovarian cancer was significantly higher than that in normal tissues, and the difference was statistically significant. Compared with patients with lower expression of SNHG16, patients with higher expression of SNHG16 had higher tumor stage, high rate of distant metastasis and low overall survival rate. Compared with the negative control si-NC group, the cell proliferation, invasion and migration ability in SNHG16 knockdown group (si-SNHG16) significantly decreased. Western Blot showed that after knockdown of SNHG16, expressions of P-AKT and MMP9 decreased significantly, while there was no significant change in the total AKT level. SNHG16 was highly expressed in ovarian cancer, and was correlated with staging, distant metastasis and poor prognosis of ovarian cancer. SNHG16 may activate phosphorylation of AKT and upregulate the expression of MMP9 to promote cell proliferation, invasion and migration of ovarian cancer.

The Long Non-Coding RNA SNHG1 Attenuates Cell Apoptosis by Regulating miR-195 and BCL2-Like Protein 2 in Human Cardiomyocytes

Background/Aims: Long non-coding RNAs (lncRNAs) are theorized to play key roles in the development of heart diseases. However, the role of lncRNAs in cardiomyocyte apoptosis is largely unknown. The present study examined the role of lncRNA SNHG1 in the human cardiomyocytes (HCMs) apoptosis and explored the underlying molecular mechanisms. Methods: SNHG1, miR-195 and mRNA expression was detected by qRT-PCR; protein level was determined by western blot; cell viability was detected by MTT assay; cell apoptosis was evaluated by flow cytometry and caspase-3 activity assay; the interaction between SNHG1 and miR195 was examined by using luciferase reporter assay. Results: Hydrogen peroxide (H₂O₂) treatment significantly suppressed cell viability and increased cell apoptotic rate and caspase-3 activity in HCMs. Overexpression of SNHG1 attenuated the effects of H₂O₂ on HCMs viability and apoptosis; while SNHG1 exerted the opposite effects. SNHG1 was found to sponge miR-195 and suppress the expression of miR-195 in HCMs. Overexpression of miR-195 suppressed cell viability and induced apoptosis in HCMs, and miR-195 was found to negatively regulate the expression of BCL-2 like protein 2 (BCL2L2) via targeting its 3’ untranslated region. Overexpression of BCL2L2 partially reversed the effects of miR-195 overexpression on cell viability and cell apoptosis of HCMs. MiR-195 overexpression or BCL2L2 knockdown attenuated the effects of SNHG1 overexpression on cell viability, cell apoptosis and protein levels of cleaved caspase-3, cleaved caspase-9 and Bax in H₂O₂-treated HCMs. Conclusion: Our results suggest a novel SNHG1/miR-195/BCL2L2 axis in the regulation of cardiomyocyte apoptosis. Modulation of SNHG1 may represent a novel strategy to treat cardiomyocyte apoptosis-related heart diseases.

Enhanced expression of the long non-coding RNA SNHG16 contributes to gastric cancer progression and metastasis.

This paper aimed to probe into the expression of long non-coding RNA (lncRNA) SNHG16 in human gastric cancer (GC) and its potential tumor biological functions. The expression of lncRNA SNHG16 was detected in GC and adjacent tissues and GC cell lines using qRT-PCR. GC MGC-803 cells were transfected with siRNA of lncRNA SNHG16, as well as blank and negative control. A series of experiments including CCK-8, flow cytometry, transwell, and wound healing assay were adopted to evaluate the effects of lncRNA SNHG16 on cell growth and metastasis. Besides, the nude mouse xenograft tumor model was established to draw tumor growth curve and measure tumor volume during treatments. TUNEL staining was used to determine the apoptosis rate of tissues. The expression of lncRNA SNHG16 in GC tissue, significantly associated with invasion depth, lymph node metastasis, TNM stage and histological differentiation (all P< 0.05), was upregulated compared with adjacent tissues. Transfected with siRNA of lncRNA SNHG16 inhibited GC MGC-803 cell proliferation, and arrested cells in the G0/G1 phase, and then promoted apoptosis rate with reduced cell invasion and shortened migration distance. Additionally, the nude mice xenograft presented lower tumor growth rate and weight loss alongside elevated apoptosis rate of tumor tissues. LncRNA SNHG16 is highly expressed in GC, while suppression of SNHG16 expression can inhibit proliferation, weaken invasion and migration of GC cells, and enhance apoptosis, to be a novel target for GC clinical treatment.

Long noncoding RNA SNHG15 promotes human breast cancer proliferation, migration and invasion by sponging miR-211-3p

Long non-coding RNAs (lncRNA) have been demonstrated to act as essential regulators in the development and progression of breast cancer. In our study, we found that long noncoding RNA SNHG15 was highly expressed in breast cancer tissues and cell lines. And the expression of SNHG15 was correlated with TNM stage, lymphnode metastasis and survival in breast cancer patients. SNHG15 knockdown significantly inhibited the proliferation and induced apoptosis in breast cancer cells in vitro and in vivo. Besides, SNHG15 downregulation suppressed cell migration and invasion in MCF-7 and BT-20 cells, and inhibited epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG15 acted as a competing endogenous RNA to sponge miR-211-3p, which was downregulated in breast cancers and inhibited cell proliferation and migration. Our results showed that there was a negative correlation between SNHG15 and miR-211-3p expression in breast cancer patients. Collectively, we, for the first time, revealed the functions of SNHG15 and miR-211-3p in breast cancer.

WITHDRAWN: SNHG16 indicates a poor prognosis and affects cell proliferation, migration and invasion in non-small cell lung cancer

Abstract In this study, we report that long non-coding RNA (lncRNA) SNHG16 is upregulated in non-small cell lung cancer (NSCLC) tissues, and is correlated 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. In vitro experiments show that SNHG16 knockdown inhibits NSCLC cell proliferation, migration and invasion, and SNHG16 overexpression promotes NSCLC cell proliferation, migration and invasion. We further identify and confirm that miR-146a is 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 might be involved in the oncogenic activity of SNHG16-miR-146a axis in NSCLC. In vivo experiments also confirm these conclusions. Taken together, the present 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 in the future.

The long noncoding RNA SNHG1 promotes tumor growth through regulating transcription of both local and distal genes.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) have important roles in various physiological processes and dysfunction of lncRNAs could be a prevalent cause in human diseases. Here we functionally characterized the nuclear-enriched lncRNA SNHG1, which is highly expressed in multiple types of cancer. We also provide evidence that SNHG1 promotes cancer cell growth by regulating gene expression both in cis and in trans. SNHG1 was involved in the AKT signaling pathway as it promotes the neighboring transcription of the protein-coding gene SLC3A2 in cis by binding the Mediator complex to facilitate the establishment of enhancer-promoter interaction. In trans, SNHG1 directly interacted with central domain of FUBP1 and antagonize the binding of FBP-interacting repressor to FUBP1, thereby coordinating the expression of the oncogene MYC. Collectively, our findings demonstrate that lncRNA SNHG1 can function both in cis and in trans with distinct mechanisms to regulate transcription, promoting tumorigenesis and cancer progression.

Long non-coding RNA SNHG15 inhibits P15 and KLF2 expression to promote pancreatic cancer proliferation through EZH2-mediated H3K27me3.

Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to be up-regulated in gastric cancer and hepatocellular carcinoma, exerting oncogenic effects. Nevertheless, the biological function and regulatory mechanism of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported that SNHG15 expression was also upregulated in PC tissues, and its overexpression was remarkably associated with tumor size, tumor node metastasis (TNM) stage and lymph node metastasis in patients with PC. SNHG15 knockdown inhibited proliferative capacities and suppressed apoptotic rate of PC cells in vitro, and impaired in-vivo tumorigenicity. Additionally, RNA immunoprecipitation (RIP) assays showed that SNHG15 epigenetically repressed the P15 and Kruppel-like factor 2 (KLF2) expression via binding to enhancer of zeste homolog 2 (EZH2), and chromatin immunoprecipitation assays (CHIP) assays demonstrated that EZH2 was capable of binding to promoter regions of P15 and KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). Furthermore, rescue experiments indicated that SNHG15 oncogenic function partially involved P15 and KLF2 repression. Consistently, an inverse correlation between the expression of SNHG15 and traget genes were found in PC tissues. Our results reported that SNHG15 could act as an oncogene in PC, revealing its potential value as a biomarker for early detection and individualized therapy.

LncRNA-SNHG1 contributes to gastric cancer cell proliferation by regulating DNMT1

ObjectiveThe objective of this study was to determine the expression of long-chain non-coding RNA SNHG1 (lncRNA-SNHG1) in gastric carcinoma and explore its function on cancer cell proliferation. MethodsThe expression of lncRNA-SNHG1 in tumor tissues and corresponding adjacent tissues from 50 patients with gastric cancer was detected with realtime-PCR. The relationships between the expression of lncRNA-SNHG1 and clinicopathological features of gastric cancer patients were analyzed. Survival analysis was performed to study the correlation between lncRNA SNHG1 expression and patient prognosis. To assess the effect of LncRNA SNHG1 on proliferation in cancer cells, cell viability and colony formation assays were conducted when lncRNA SNHG1 was upregulated or downregulated by Lentivirus or plasmid in gastric cancer cells. Furthermore, in vivo tumor assay was performed to confirm the impact of lncRNA SNHG1 on proliferation of gastric cancer. ResultsThe expression of lncRNA SNHG1 in gastric cancer tissues was significantly higher than that in adjacent tissues and was correlated with TNM stage, T stage, and lymph node metastasis. The survival time of patients with higher expression level of lncRNA-SNHG1 was significantly lower than that of the lower expression level. LncRNA-SNHG1 accelerated the proliferation of gastric cancer cells obviously and increased the expression of DNMT1. ConclusionLncRNA SNHG1 promotes DNMT1 expression, which facilitates the gastric cancer proliferation.

Down-regulated long non-coding RNA SNHG1 inhibits tumor genesis of colorectal carcinoma.

Colorectal carcinoma (CRC) is the vital cancer mortality worldwide and the long noncoding RNAs (lncRNAs) is considered as an important biomarker. The aim of this study was to examine the influence of lncRNA-SNHG1in CRC, and explore the relationship of lncRNA-SNHG1 and CRC, and consequently find a new therapeutic target for CRC patients. This study used 80 CRC patients and several cancer cell lines, with RNA interference technology to find the function of SNHG1. SNHG1 expression was higher in CRC tissue lines other than the cancer adjacent tissues. Moreover, down-regulated SNHG1 resulting in smaller tumor size and lighter tumor weight. Additionally, down-regulated SNHG1 inhibited cell migration, proliferation and colony formation, but promoted cell apoptosis. Our findings revealed that down-regulated SNHG1 could inhibit CRC tumor genesis and SNHG1 might act as an important potential therapeutic target in CRC treatment.

Long Non-Coding RNA SNHG6 as a Potential Biomarker for Hepatocellular Carcinoma.

Long Non-coding RNAs (lncRNAs) refer to all non-protein coding transcripts longer than 200 nucleotides. Their critical roles in different biological pathways have been already well established. Altered expression of lncRNAs can be involved in the cancer initiation and/or progression. Since patients with hepatocellular carcinoma (HCC) are usually diagnosed in late stages, developing diagnostic methods seems to be essential. In this study, the expression levels of different lncRNAs were systematically analysed in different genomic and transcriptome datasets. The analyses showed that SNHG6 is among the lncRNAs with distinctive dysregulation of expression and copy number variation in HCC tumors compared with normal tissues. The results also suggest that the dysregulation of SNHG6 is highly cancer type specific. Through co-occurrence analyses, we found that SNHG6 and its related co-expressed genes on 8q are involved in the structural integrity of ribosome and translation. This comprehensive in silico analysis, provides a resource for investigating SNHG6 in hepatocellular carcinoma and lays the groundwork for design of next researches.

Long non-coding RNA SNHG1 regulates zinc finger E-box binding homeobox 1 expression by interacting with TAp63 and promotes cell metastasis and invasion in Lung squamous cell carcinoma

The long non-coding RNAs (lncRNAs) have been recently shown to participate in the progression of a variety of cancers. However, the biological role of lncRNAs and the underlying mechanisms in Lung squamous cell carcinoma (SCC) or lung adenocarcinoma (AD) remain unclear. Herein, we investigated expression of 5 lncRNAS (SNHG1, NCBP2-AS2, LINC01206, SOX2-OT and LINC01419) in SCC and AD tissues. SNHG1 was one of over-expressed lncRNAs in SCC tissues. Knockdown of SNHG1 significantly inhibited the proliferation, metastasis, invasive ability and induced apoptosis of SCC cells. Moreover, SNHG1 affected the expression of zinc finger E-box binding homeobox 1(ZEB1), which has also been observed to be up-regulated in SCC and to promote cell metastasis and invasion. Rather than direct interaction, SNHG1 regulated ZEB1expression by suppressing the activity of p63 TA isoform (TAp63), which is a repressor of ZEB1 and physically associates with SNHG1. Furthermore, SNHG1 promoted ZEB1 expression and promoted cell proliferation, metastasis, invasive but inhibited apoptosis of SCC cells via the TAp63/ZEB1 pathway. Taken together, our findings suggested that SNHG1 might play an oncogenic role in SCC through ZEB1 signaling pathway by inhibiting TAp63 and might serve as a valuable prognostic biomarker and therapeutic target for SCC patients.

Long non-coding RNA SNHG14 promotes microglia activation by regulating miR-145-5p/PLA2G4A in cerebral infarction

Activated microglia cells (MCs) are able to release a large amount of inflammatory cytokines after ischemic stroke, which exacerbates neuron damage. In this study, we explored the functional involvement of long non-coding RNA (lncRNA) SNHG14 and its potential regulatory mechanism in the activation of MCs. The mouse model of middle cerebral artery occlusion (MCAO) and microglia cell model of oxygen/glucose deprivation (OGD) were made. The expression of SNHG14, miR-145-5p and PLA2G4A protein expression was determined by quantitative real time PCR and western blot, respectively. Dual-luciferase assay was used to verify the direct binding of miR-145-5p and PLA2G4A. Flow cytometry was applied to measure neurons’ apoptosis. SNHG14 highly expressed in ischemic cerebral tissues and BV-2 cells after OGD treatment. SNHG14 knockdown could remarkably inhibit BV-2 cells activation induced by OGD; while SNHG14 overexpression significantly promoted BV-2 cells activation, showing an increase of TNF-α and NO production and neurons’ apoptosis rate. Additionally, SNHG14 knockdown promoted the expression of miR-145-5p and reduced PLA2G4A. Contrarily, SNHG14 overexpression inhibited miR-145-5p expression and increased PLA2G4A. Moreover, miR-145-5p overexpression also reversed the effect of OGD on BV-2 cells activation. Bioinformatics analysis and dual-luciferase assay supported that SNHG14 could bind directly to miR-145-5p and miR-145-5p-binding site was existed on 3′-UTR of PLA2G4A. MiR-145-5p mimic reversed the increase of PLA2G4A and reduced the high levels of TNF-α and NO in BV-2 cells induced by SNHG14 overexpression. SNHG14 increased the expression of PLA2G4A by inhibition of miR-145-5p, which resulted in the activation of MCs in cerebral infarction.

Long non-coding RNA SNHG17 is an unfavourable prognostic factor and promotes cell proliferation by epigenetically silencing P57 in colorectal cancer.

Recently, substantial evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in multiple cancers including colorectal cancer (CRC). Utilizing publicly available lncRNA-expression-profiling data from the Gene Expression Omnibus (GEO) dataset GSE21510, we screened SNHG17 as a new candidate lncRNA associated with CRC development and progression. We further demonstrated that SNHG17 was upregulated in CRC tissues, and that its overexpression was significantly correlated with tumor size, TNM stage, and lymph node metastasis in CRC patients. Moreover, SNHG17 knockdown significantly inhibited the proliferation of CRC cells, and induced cell cycle G1/G0 phase arrest and cell apoptosis. Consistent with these findings, SNHG17 silencing inhibited tumor growth in vivo. Mechanistic studies revealed the capability of lncRNA SNHG17 to epigenetically suppress P57 by binding to enhancer of zeste homolog 2 (a key component of polycomb repressive complex 2) in CRC cells, and quantitative real-time polymerase chain reaction assays demonstrated that SNHG17 expression levels were inversely correlated with those of P57 in CRC tissues. Furthermore, rescue experiments confirmed that SNHG17 exerted oncogenic functions partly through regulating P57 expression. These findings represent the first reporting of the roles and mechanisms associated with SNHG17 in CRC progression, highlighting SNHG17 as a potential therapeutic target for CRC patients.

Upregulated expression of long noncoding RNA SNHG15 promotes cell proliferation and invasion through regulates MMP2/MMP9 in patients with GC.

Accumulation of data indicates that misregulated long noncoding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be served as diagnosis and prognosis biomarker or potential therapeutic targets. Identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are significant for understanding the development and progression of cancer. In this study, we identified a novel lncRNA SNHG15, whose expression was upregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, increased SNHG15 expression was positively correlated with invasion depth (P < 0.001), advanced tumor node metastasis (TNM) stage (P = 0.001), and lymph node metastasis (P = 0.019). SNHG15 levels were robust in differentiating GC tissues from controls (area under the curve (AUC) = 0.722; 95% confidence interval (CI) = 0.657-0.782, P < 0.01). Kaplan-Meier analysis demonstrated that elevated SNHG15 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that SNHG15 could be an independent prognostic marker. Furthermore, knockdown of SNHG15 expression by siRNA could inhibit cell proliferation and invasion and induce apoptosis, while ectopic expression of SNHG15 promoted cell proliferation and invasion in GC cells partly via regulating MMP2 and MMP9 protein expression. Our findings present that elevated lncRNA SNHG15 could be identified as a poor prognostic biomarker in GC and regulate cell invasion.