Long noncoding RNA small nucleolar RNA host genes as prognostic molecular biomarkers in hepatocellular carcinoma: A meta-analysis.

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.

LncRNA SNHG7 accelerates the proliferation, migration and invasion of hepatocellular carcinoma cells via regulating miR-122-5p and RPL4

LncRNA SNHG16 promotes proliferation, migration and invasion of osteosarcoma cells by targeting miR-1301/BCL9 axis

Background: The aim of this study was to investigate the correlation of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) with the prognosis in breast cancer patients, and its effect on breast cancer cell proliferation and apoptosis. Methods: A total of 178 breast cancer patients were consecutively recruited, then tumor tissue and the paired adjacent tissue were obtained during surgery for lncRNA SNHG1 determination by quantitative polymerase chain reaction (qPCR). LncRNA SNHG1 expression was also measured in breast cancer cell lines and normal breast epithelial cell line. Subsequently, negative control (NC) overexpression plasmids, lncRNA SNHG1 overexpression plasmids, NC short hairpin RNA (shRNA) plasmids and lncRNA SNHG1 shRNA plasmids were transfected into MDA-MB-453 cells as well as MCF7 cells, and cell proliferation and apoptosis were measured afterward. Results: LncRNA SNHG1 expression in tumor tissue was increased compared with paired adjacent tissue, and it correlated with higher T stage and worse overall survival (OS) in breast cancer patients. LncRNA SNHG1 expression was also elevated in breast cancer cell lines compared with normal breast epithelial cell line. Cell Counting Kit-8 (CCK8) assay revealed that lncRNA SNHG1 overexpression promoted while lncRNA SNHG1 shRNA reduced cell proliferation, and Annexin V-fluorescein isothiocyanate/propidium iodide staining (AV/PI) assay illustrated that lncRNA SNHG1 overexpression decreased while lncRNA SNHG1 shRNA increased cell apoptosis rate. In addition, Western Blot assay disclosed that lncRNA SNHG1 overexpression downregulated while lncRNA SNHG1 shRNA upregulated pro-apoptotic marker (C-Caspase3) expression, and lncRNA SNHG1 overexpression increased while lncRNA SNHG1 shRNA decreased anti-apoptotic marker (p-P38) expression. Conclusions: LncRNA SNHG1 is upregulated in tumor tissue and correlates with higher T stage and worse OS, and it promotes cell proliferation but inhibits cell apoptosis in breast cancer.

The involvement of long non-coding RNA (LncRNAs) in HCC development has been widely recognized in recent decades. LncRNA small nucleolar RNA host gene 5 (SNHG5) has been identified to be implicated in the development of many tumors, and this study aimed to explore the role of SNHG5 in HCC tumorigenesis. The expression levels of SNHG5, miR-363-3p, and Ring Finger Protein 38 (RNF38) were measured by using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) or Western blot assay, respectively. Cell proliferation was analyzed by MTT assay. Flow cytometry was used to investigate cell apoptosis. Cell migration and invasion abilities were detected by transwell assay. The relationship among SNHG5, miR-363-3p, and RNF38 was confirmed using bioinformatics analysis and Luciferase reporter assay. The expression of SNHG5 and RNF38 was elevated in HCC tissues and cell lines, and highly expressed SNHG5 and RNF38 could induce apoptosis and repress proliferation, migration, as well as invasion in HCC cells. Further investigations showed that SNHG5 might act as a competing endogenous RNA of miR-26a-5p and thereby cause the derepression of the downstream target RNF38. Moreover, rescue experiments indicated that SNHG5 silence inhibited the progression of HCC cells by regulating miR-363-3p, and the facilitated effects of RNF38 in the progression of HCC cells were regulated by miR-363-3p. LncRNA SNHG5 may promote human HCC progression by regulating the miR-363-3p/RNF38 axis, providing a novel insight into the pathogenesis of HCC and therapeutic strategy for HCC treatment.

Hepatocellular carcinoma (HCC) is a malignant tumor with high mortality and severe complication in China. Numerous studies have shown that long noncoding RNAs (lncRNAs) are involved in the regulation of various processes in cancer cells. Our research aimed to investigate the underlying mechanism of the lncRNA small nucleolar RNA host gene 7 (SNHG7) in HCC development. The expression of SNHG7, microRNA-122-5p (miR-122-5p), and Forkhead box K2 (FOXK2) was assessed via quantitative real-time polymerase chain reaction. 3-(4,5) -dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and transwell assays were performed to measure cell viability, migration, and invasion, respectively. The relative protein levels were detected by Western blot. The relationships between miR-122-5p and SNHG7 or FOXK2 were predicted by online software and then confirmed by dual-luciferase reporter assay. Animal experiments were conducted to clarify the effects of SNHG7 on proliferation in vivo. To begin with, SNHG7 was upregulated, while miR-122-5p was downregulated in HCC tissues and cells. Downregulation of SNHG7 inhibited cell growth and metastasis. Interestingly, SNHG7 could abolish the effects of miR-122-5p on HCC cells. Furthermore, miR-122-5p targeted FOXK2 and miR-122-5p recovered the effects of FOXK2 downregulation on cell growth and metastasis in HCC cells. Besides, SNHG7 facilitated HCC tumor growth in vivo through the miR-122-5p/FOXK2 axis. The lncRNA SNHG7 boosted the development of HCC by regulating FOXK2 through sponging miR-122-5p.

Hepatocellular carcinoma (HCC) is considered as a common malignancy worldwide. Considerable evidence has illustrated that abnormally expressed long noncoding RNAs (lncRNAs) are in a close correlation with the initiation and progression of various tumors, including HCC. LncRNA small nucleolar RNA host gene 22 (SNHG22) has been reported to play important roles in tumor initiation, but its role and mechanism are little known in HCC. In our report, we discovered the high level of SNHG22 in HCC tissues and cells, and the high expression of SNHG22 was correlated with unfavorable clinical outcome in HCC patients. Functional assays implied that SNHG22 deficiency suppressed cell proliferation, migration, invasion, and angiogenesis in vitro. Additionally, it was also confirmed that silenced SNHG22 suppressed tumor growth and angiogenesis in vivo. Mechanistic exploration revealed that SNHG22 recruited DNMT1 to miR-16-5p DNA promoter through EZH2 and inhibited miR-16-5p transcription via DNA methylation. Finally, we verified that the suppression of miR-16-5p countervailed the suppressive effect of SNHG22 deficiency on HCC cell proliferation, migration, invasion, and angiogenesis. Conclusively, this study clarified the SNHG22/EZH2/DNMT1/miR-16-5p axis and revealed that SNHG22 could be an underlying biomarker for HCC.

Neuropathic pain is an intractable comorbidity of spinal cord injury. Increasing noncoding RNAs have been implicated in neuropathic pain development. lncRNAs have been recognized as significant regulators of neuropathic pain. lncRNA Small Nucleolar RNA Host Gene 4 (SNHG4) is associated with several tumors. However, the molecular mechanisms of SNHG4 in neuropathic pain remain barely documented. Here, we evaluated the function of SNHG4 in spinal nerve ligation (SNL) rat models. We observed that SNHG4 was significantly upregulated in SNL rat. Knockdown of SNHG4 was able to attenuate neuropathic pain progression via regulating behaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, knockdown of SNHG4 could repress the neuroinflammation via inhibiting IL-6, IL-12, and TNF-α while inducing IL-10 levels. Additionally, miR-423-5p was predicted as the target of SNHG4 by employing bioinformatics analysis. miR-423-5p has been reported to exert significantly poorer in several diseases. However, the role of miR-423-5p in the development of neuropathic pain is needed to be clarified. Here, in our investigation, RIP assay confirmed the correlation between miR-423-5p and SNHG4. Meanwhile, we found that miR-423-5p was significantly decreased in SNL rat models. SNHG4 regulated miR-423-5p expression negatively. As exhibited, the loss of miR-423-5p contributed to neuropathic pain progression, which was rescued by the silence of SNHG4. Therefore, our study indicated SNHG4 as a novel therapeutic target for neuropathic pain via sponging miR-423-5p.

Intervertebral disc (IVD) degeneration (IDD) is a well-known consequence of low back pain, as characterized by aberrant cell proliferation and apoptosis of nucleus pulposus (NP) cells. In the present study, we aimed to investigate the effect of lncRNA small nucleolar RNA host gene 6 (SNHG6) on deregulated functions of degenerative NP cells. After the establishment of rat IDD models, the mRNA and protein levels of collagen-I (Col-I) and collagen II (Col-II), and mRNA level of SNHG6 were detected by using reverse transcription quantitative Real Time-PCR (RT-qPCR) and Western blot. We further investigated the role and molecular mechanisms of SNHG6 by overexpressing or silencing it in degenerative NP cells. Cell proliferation was measured by MTT assay and EdU staning, and apoptosis was measured by flow cytometry. The target of SNHG6 was identified by starBase and Dual-Luciferase reporter assay. Upregulation of SNHG6 was found in IDD NP cells than in normal cells, associated with higher level of Col-I and lower level of Col-II. Overexpression of SNHG6 inhibited cell proliferation and enhanced apoptosis, accompanied by increased expression of Bax, caspase-3, and p21, as well as decreased expression of Bcl-2, which was in reverse to the treatment of SNHG6 silencing. Moreover, miR-101-3p was indicated as a target of SNHG6, and inhibition of miR-101-3p reversed the effects on proliferation and apoptosis induced by SNHG6. SNHG6 suppressed cell proliferation and induced apoptosis by increasing expression of Bax, caspase-3, p21 and decreasing Bcl-2 through targeting miR-101-3p, which suggested that SNHG6 could be a potential target in the treatment of IDD.

Background: Long noncoding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides in length. They drive many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, RNA and protein. Recent studies have identified numerous lncRNAs active in colorectal cancer (CRC). The lncRNA small nucleolar RNA host gene 6 (SNHG6) has been reported to have an oncogenic role in multiple cancers. However, the biological role and mechanism of SNHG6 in the tumorigenesis of CRC has not been reported in-deep.Methods: The Cancer Genome Atlas (TCGA) database and GEO database were used to identify SNHG6 expression in different human cancers and explore the relationship between SNHG6 expression and patient prognosis using Kaplan-Meier method analysis. SNHG6 expression in 77 pairs of clinical CRC tissues and different CRC cell lines were analyzed by quantitative real-time PCR (qRT-PCR). A CCK-8 assay was used to assess cell proliferation, transwell assay to detect the cell metastasis, and tumor growth was investigated with a nude mice model in vivo. Whether UPF1 and ZEB1 are downstream targets of SNHG6 was verified by bioinformatics target gene prediction, qRT-PCR and western blot.Results: TCGA data showed that SNHG6 was significantly upregulated in colorectal cancer samples in comparison with healthy data samples (P < 0.01). CRC patients with high levels of SNHG6 had a significantly shorter overall survival than those with low levels of SNHG6 (P = 0.0162). qRT-PCR confirmed that the expression of SNHG6 was significantly upregulated in CRC tissues and cell lines. Upregulation of SNHG6 expression induced RKO and HCT116 cell proliferation as well as RKO cell metastasis, while downregulation of SNHG6 expression supressed the proliferation and metastasis of RKO cells and tumor growth in vivo. UPF1 was upregulated and ZEB1 was decreased when SNHG6 knockdown, regulating the TGF-β/Smad pathway and inducing EMT respectively.Conclusions: SNHG6 may play an oncogenic role in CRC cells by activating TGF-β/Smad signaling pathway via targeting of UPF1 and inducing EMT via regulating ZEB1. This could be a prognostic biomarker and therapeutic target for CRC.

Colon cancer is the main cause of cancer mortality worldwide. Its poor prognosis is mainly ascribed to high recurrence rates. Identifying novel prognostic biomarkers and therapeutic key points for management is crucial and important. Long non-coding RNAs (lncRNAs) are a class of RNAs, which have various roles in carcinogenicity and molecular mechanisms. The lncRNA small nucleolar RNA host gene 1 (SNHG1) contributes to the promotion of tumor development, however, the connections between SNHG1 and colon cancer are still unclear. The aim of the present study was to investigate the clinical significance, the biological functions, and the potential mechanism of SNHG1 in colon cancer. In the present study, we referred to the Oncomine database and used RT-qPCR to determine that SNHG1 expression was significantly higher both in colon cancer tissues and cancerous cell lines than in normal samples. Cell functional experiments were performed after knockdown of SNHG1, including Cell Counting Kit-8 assay, colony formation assay, Transwell® assay, and flow cytometric analyses of cell apoptosis, which suggested that SNHG1 stimulated colon cancer cell proliferation, promoted cell invasion and migration, and inhibited apoptosis. Immunohistochemical staining and western blotting experiments revealed that in colon cancer cells with SNHG1 knockdown, β-catenin, c-Myc and cyclin D1 protein levels were decreased, while E-cadherin was increased, which suggested that SNHG1 promoted colon cancer cell proliferation, migration and invasion through the Wnt/β-catenin signaling pathway. Our results indicated that SNHG1 and its interrelated components may be future therapeutic targets of carcinoma of the colon.

Objective To investigate the expression level of small nucleolar RNA host gene 12 (SNHG12) in hepatocellular carcinoma (HCC) tissue and its mechanism on the growth and invasion of hepatoma cells. Methods We determined the expression level of SNHG12 in 50 HCC patients collected from Zhongnan Hospital of Wuhan University with real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and then studied its clinical significance. SiRNA interference was used to knock down the SNHG12 level in vitro. In addition, Transwell assay and methyl thiazol tetrazolium (MTT) assay were uesd to observe the changes in growth and invasion of hepatoma cells. Western blotting was used to detecte the change of key molecules in transforming growth factor-β (TGF-β)/Smad pathway after SNHG12 was silenced. Results SNHG12 was upregulated in HCC tissues (2.943±0.881) as compared with adjacent tissues (1.613±0.533, P=0.007). HCC patients whose tumor diameter >5 cm had a higher SNHG12 level (4.024±0.281) than those with tumor diameter ≤5 cm (2.591±0.394, P=0.002). HCC patients with a higher Edmonson-Steiner grade had a higher SNHG12 level (P=0.001). SNHG12 was closely associated with tumor diameter (P=0.000), Edmonson-Steiner grade (P=0.003) and metastasis (P=0.031). Furthermore, Kaplan-Meier and Log-rank test analyses suggested that HCC patients with high SNHG12 expression had shorter overall survival (P=0.009) and higher recurrence rate than those with low expression of SNHG12 (P=0.001). SNHG12 promoted hepatoma cell growth and invasion by regulating the TGF-β/Smad pathway. Conclusion These findings indicate that SNHG12 is a critical molecule for HCC progression and is potentially a new effective target for HCC therapy. Key words: Carcinoma, hepatocellular; Small nucleolar RNA host gene 12; Growth; Invasion

BackgroundThe pivotal role of long noncoding RNAs (lncRNAs) in cancer immune responses has been well established. This study was conducted with the aim of exploring the molecular mechanism of lncRNA small nucleolar RNA host gene 12 (SNHG12) in immune escape of non-small cell lung cancer (NSCLC).MethodsExpression of lncRNA SNHG12, programmed cell death receptor ligand 1 (PD-L1), ubiquitin-specific protease 8 (USP8), and human antigen R (HuR) in NSCLC tissues and cells was measured, and their binding relationship was determined. NSCLC cell proliferation and apoptosis were assessed. Peripheral blood mononuclear cells (PBMCs) were co-cultured with NSCLC cells. The ratio of CD8+ T cells, PBMC proliferation, and inflammatory factors were determined. lncRNA SNHG12 localization was assessed via subcellular fractionation assay. The half-life period of mRNA was determined using actinomycin D. Xenograft tumor models were established to confirm the role of lncRNA SNHG12 in vivo.ResultsLncRNA SNHG12 was found to be prominently expressed in NSCLC tissues and cells, which was associated with a poor prognosis. Silencing lncRNA SNHG12 resulted in the reduction in proliferation and the promotion of apoptosis of NSCLC cells, while simultaneously increasing PBMC proliferation and the ratio of CD8+ T cells. Mechanically, the binding of lncRNA SNHG12 to HuR improved mRNA stability and expression of PD-L1 and USP8, and USP8-mediated deubiquitination stabilized the protein level of PD-L1. Overexpression of USP8 or PD-L1 weakened the inhibition of silencing lncRNA SNHG12 on the immune escape of NSCLC. Silencing lncRNA SNHG12 restricted tumor growth and upregulated the ratio of CD8+ T cells by decreasing USP8 and PD-L1.ConclusionLncRNA SNHG12 facilitated the immune escape of NSCLC by binding to HuR and increasing PD-L1 and USP8 levels.

BackgroundRecent evidence has found that lncRNA small nucleolar RNA host gene 16 (SNHG16) was associated with cell carcinogenesis in NSCLC. Here, we further investigated the precise functions and mechanisms of SNHG16 in NSCLC progression.MethodsThe expression of SNHG16, microRNA (miR)‐520a‐3p and EPH Receptor A2 (EphA2) was measured using quantitative real‐time polymerase chain reaction and western blot, respectively. Cell proliferation was determined using 3‐(4, 5)‐dimethylthiahiazo (−z‐y1)‐3, 5‐di‐phenytetrazoliumromide (MTT) assay. The migrated and invaded cells were measured by Transwell assay. Flow cytometry was used to detect apoptotic cells. The interaction between miR‐520a‐3p and SNHG16 or EphA2 was confirmed using a dual‐luciferase reporter assay.ResultsWe found that SNHG16 was upregulated in NSCLC tissues and cell lines, knockdown of SNHG16 inhibited cell proliferation, migration, invasion and induced apoptosis in vitro as well as suppressed tumor growth in vivo. MiR‐520a‐3p directly bound to SNHG16 and miR‐520a‐3p, and SNHG16 acted as a ceRNA in regulating EphA2 through competitively binding to miR‐520a‐3p. Additionally, rescue assay exhibited the anticancer activity mediated by SNHG16 knockdown on NSCLC could be reversed by miR‐520a‐3p inhibition or EphA2 overexpression.ConclusionSNHG16 promoted NSCLC development by regulating the miR‐520a‐3p/EphA2 axis, suggesting novel insights for the pathogenesis of NSCLC and new potential therapeutic targets for the treatment of NSCLC.Key points Knockdown of SNHG16 inhibited NSCLC cell proliferation, migration, invasion and induced apoptosis in vitro as well as suppressed tumor growth in vivo. SNHG16 directly interacted with miR‐520a‐3p.EphA2 was a target of miR‐520a‐3p.SNHG16 could regulate the expression of EphA2 by binding to miR‐520a‐3p.SNHG16 promoted NSCLC development by regulating the miR‐520a‐3p/EphA2 axis.

Renal cell carcinoma (RCC) is a primary malignant kidney cancer subtype. It has been suggested that long non-coding RNAs (lncRNAs) serve important roles in the progression of kidney cancer. In fact, the lncRNA small nucleolar RNA host gene 12 (SNHG12) was discovered to be overexpressed in various types of cancer. However, to the best of our knowledge, the role of SNHG12 in RCC remains unclear. The present study aimed to investigate the function of SNHG12 and its underlying molecular mechanism of action in RCC. In patient samples and datasets from The Cancer Genome Atlas. Reverse transcription-quantitative PCR, demonstrated that SNHG12 expression levels were upregulated in RCC tumor tissues, but not in normal kidney tissues. SNHG12 upregulation was also observed in RCC cell lines. Kaplan-Meier survival analysis indicated a poor prognosis for those patients with RCC who had upregulated SNHG12 expression levels. Following lentivirus transduction, SNHG12 was successfully knocked down (validated by western blot analysis) and cell migration and invasion assays were performed. SNHG12 knockdown markedly inhibited cell viability and invasion, while increasing apoptosis in both A498 and 786O cell lines. The results of the luciferase reporter assay suggested that SNHG12 exerted its role by sponging microRNA (miR)-200c-5p, which led to the upregulation of its target gene, collagen type XI α1 chain (COL11A1). This was further validated, as miR-200c-5p inhibition reduced the effects of SNHG12 downregulation on cell viability and apoptosis, without affecting SNHG12 expression levels. Furthermore, the findings indicated that SNHG12 may partially exert its role through COL11A1, which was also upregulated in RCC. In conclusion, the results of the present study suggested that the SNHG12/miR-200c-5p/COL11A1 axis may be crucial for RCC progression, which provided an insight into potential therapeutic strategies for RCC treatment.