Small Nucleolar RNA Host Gene Research Articles

LncRNA SNHG17 regulates cell proliferation and invasion by targeting miR-338-3p/SOX4 axis in esophageal squamous cell carcinoma

Small nucleolar RNA host gene 17 (SNHG17), a novel functional long noncoding RNA, has been demonstrated to play an essential role in the oncogenesis of several tumors. However, for esophageal squamous cell carcinoma (ESCC) the expression pattern and detailed function of SNHG17 are largely unknown. Hence, we conducted this study to explore potential roles and underlying oncogenic mechanisms for SNHG17 in ESCC progression. Results demonstrated SNHG17 to be markedly upregulated in ESCC. Knockdown of SNHG17 significantly suppressed ESCC cell proliferation, invasion, and epithelial–mesenchymal transition in vitro and tumor growth in vivo. Online database software analysis found miR-338-3p to interact with SNHG17 with the level of miR-338-3p negatively correlated with SNHG17 levels in ESCC samples. Further, miR-338-3p was found to directly target SRY-box transcription factor 4 (SOX4) in ESCC cells. Mechanistic analysis suggested that SNHG17 acts as an endogenous “sponge” competing with miR-338-3p to regulate SOX4, thereby promoting tumor progression. These results suggest that these molecular interactions may be potential therapeutic targets for ESCC.

Exosome-derived SNHG16 sponging miR-4500 activates HUVEC angiogenesis by targeting GALNT1 via PI3K/Akt/mTOR pathway in hepatocellular carcinoma.

Accumulating evidence suggests cancer-derived exosomes play an important role in promoting angiogenesis. Long noncoding RNA small nucleolar RNA host gene 16 (SNHG16) is known to aggravate hepatocellular carcinoma (HCC) progression. However, the function of exosomal SNHG16 in HCC angiogenesis remains unclear. In this study, the expression of SNHG16 was significantly upregulated in HCC tissues and cell lines. The proliferative, migratory, and angiogenic abilities of HUVECs were enhanced after exposure to exosomes derived from HCC cells by transmitting SNHG16. In addition, SNHG16 was validated to promote the biological function of HUVECs directly. Exosomal SNHG16 increased GALNT1 expression to promote angiogenesis via sponging miR-4500. SNHG16/miR-4500/GALNT1 axis played an important role in exosome-mediated angiogenesis and tumor growth in vitro and vivo. Furthermore, SNHG16 activated PI3K/Akt/mTOR pathway via competing endogenous miR-4500 and GALNT1. Meanwhile, the expression of plasma exosomal SNHG16 upregulated in the plasma of HCC patients. These data elucidated the essential role of exosomal SNHG16 in communication between HCC cells and endothelial cells. Exosomal SNHG16 could be utilized as a therapeutic target for anti-angiogenesis in HCC progression.

Interference with long noncoding RNA SNHG3 alleviates cerebral ischemia-reperfusion injury by inhibiting microglial activation.

Neuroinflammation plays a strong part in cerebral ischemia-reperfusion injury, and microglial activation is regarded as a marker for neuroinflammation. Long noncoding RNA small nucleolar RNA host gene 3 (lncRNA SNHG3) is heavily expressed in cerebral ischemia-reperfusion models, but its mechanism is rarely studied. This study aims to explore whether SNHG3 is involved in cerebral ischemia-reperfusion injury by promoting microglial activation and inflammatory factor secretion. Activation of microglia was induced through oxygen-glucose deprivation/reoxygenation (OGD/R) or LPS and the cerebral ischemia-reperfusion injury in mice was induced by transient middle cerebral artery occlusion (tMCAO). Levels of SNHG3, IL-6, and TNF-α were determined by quantitative real-time PCR. Immunofluorescence was used for the detection of Iba-1 expression. Western blot was carried out for the detection of Iba-1 and histone deacetylase 3 (HDAC3) protein levels. An ELISA was performed to detect TNF-α and IL-6 levels. RNA pull-down, RNA immunoprecipitation, and co-Immunoprecipitation assays were conducted to detect the binding between SNHG3 and HDAC3. A H&E staining assay was applied to observe pathologic changes. Microglial activation was observed with immunohistochemistry. Levels of SNHG3, microglial activation marker Iba-1, proinflammatory factors (TNF-α and IL-6) were highly expressed in cell models (treated with OGD/R or LPS) and mouse models (tMCAO). Besides, SNHG3 could bind to HDAC3 and promote its expression. Through further study, we found that SNHG3 could stabilize the protein levels of HDAC3 and inhibit the ubiquitination of HDAC3. Furthermore, interference with SNHG3 down-regulated the levels of HDAC3, Iba-1, TNF-α, and IL-6, whereas the overexpression of HDAC3 reversed the results. The H&E staining assay demonstrated that the condition of vacuoles of different sizes, uneven cytoplasmic staining, and inflammatory infiltration in the brain tissue was improved by interference with SNHG3. The immunohistochemistry result showed that microglial activation marker Iba-1 was increased in the shRNA-SNHG3 group, indicating that interference with SNHG3 inhibited the activation of microglia in the brain. LncRNA SNHG3 aggravated cerebral ischemia-reperfusion injury by promoting the activation of microglia, increasing the levels of HDAC3, and the secretion of inflammatory factors.

LncRNA SNHG14 promotes the proliferation, migration, and invasion of thyroid tumour cells by regulating miR-93-5p.

Long non-coding RNAs (lncRNAs) exert vital functions in the occurrence and development of various tumours. The aim of this study was to examine the regulatory effect and underlying molecular mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) on the proliferation, invasion and migration of thyroid tumour cells. The expression of SNHG14 in thyroid tumour cell lines was determined using qRT-PCR. CCK-8 and western blot were used to detect the effects of SNHG14 on proliferation and apoptosis of thyroid tumour cells. The effect of SNHG14 on the migration and invasion of thyroid tumour cells was analyzed using immunofluorescence, wound-healing and transwell assays. A targeting relationship between SNHG14 and miR-93-5p was determined using bioinformatics software and luciferase reporter assays. In addition, CCK-8, immunofluorescence, wound-healing and transwell assays were applied to demonstrate that SNHG14 promoted the proliferation, migration and invasion of thyroid tumour cells by targeting miR-93-5p. The biological function of SNHG14 in vivo was explored through a xenograft model and immunohistochemistry. SNHG14 was upregulated in thyroid tumour cells compared with normal cells. Downregulation of SNHG14 effectively reduced the proliferation, migration and invasion of TPC-1 cells, and induced cell apoptosis. Moreover, SNHG14 directly targeted miR-93-5p and there was a negative correlation between them. Further functional experiments illustrated that miR-93-5p overexpression dramatically reversed the promoting role of SNHG14 in proliferation, migration and invasion of TPC-1 cells. Our results demonstrated that SNHG14 promotes the proliferation, invasion and migration of thyroid tumour cells by downregulating miR-93-5p.

LncRNA MEG8 is downregulated in osteoarthritis and regulates chondrocyte cell proliferation, apoptosis and inflammation

Long noncoding RNA (lncRNA) maternally expressed 8, small nucleolar RNA host gene (MEG8) has been widely reported for its pro-proliferative, anti-apoptotic and anti-inflammatory effects in diverse diseases. The aim of the present study was to investigate the effects and underlying mechanism of MEG8 on IL-1β-stimulated human osteoarthritis (OA) chondrocytes. C28/I2 chondrocytes were cultured under the stimulation of IL-1β to establish a cellular model of OA. Functional assays involving Cell Counting Kit-8 and flow cytometry were performed to determine proliferation and apoptosis in the cells. The protein expression levels of caspase-3 and inflammatory cytokines were detected using cell-based ELISA. The expression levels of PI3K/AKT pathway-related proteins were evaluated by western blotting. It was identified that MEG8 expression was increased in the cartilage of patients with OA and in IL-1β-treated C28/I2 cells. In C28/I2 cells, silencing of MEG8 expression noticeably triggered IL-1β-induced proliferation suppression, cell death and an inflammatory response. However, transfection with MEG8 displayed adverse effects. Furthermore, MEG8 overexpression prevented IL-1β-induced activation of the PI3K/AKT signaling pathway in C28/I2 cells. These data demonstrated that MEG8 exerted protective effects against IL-1β-induced apoptosis and inflammation of OA chondrocytes by regulating the PI3K/AKT signaling pathway. Thus, the present study demonstrates that MEG8 might be a promising target for the treatment of OA.

Long non-coding RNA SNHG1 relieves microglia activation by downregulating miR-329-3p expression in an in vitro model of cerebral infarction.

Following cerebral infarction, activated microglia cells can release a large amount of inflammatory cytokines, thereby exacerbating neuronal damage. It has been demonstrated that the long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) exerts a protective effect against cerebral infarction. However, its specific role in cerebral infarction and underlying mechanism have yet to be fully elucidated. The present study aimed to investigate the effects of the SNHG1 and microRNA (miR)-329-3p in cerebral infarction and to determine the underlying molecular mechanisms. An in vitro oxygen-glucose deprivation (OGD) model was established using the BV-2 microglial cell line. The mRNA expression levels of SNHG1 and miR-329-3p were analyzed using reverse transcription-quantitative PCR and the protein expression levels of cleaved caspase-3 and caspase-3 were detected using western blotting. The binding relationship between SNHG1 and miR-329-3p was predicted using starBase and verified using a dual luciferase reporter assay. The release of TNF-α and nitric oxide, as well as caspase-3 activity, were detected using appropriate commercial kits. Flow cytometry analysis was performed to measure cell apoptosis. The results of the present study revealed that the expression levels of SNHG1 were upregulated in the OGD-induced BV-2 cell model. miR-329-3p was discovered to directly target SNHG1, and its mRNA expression levels were downregulated in the OGD-induced BV-2 cell model. The SNHG1-plasmid downregulated miR-329-3p expression levels, while this effect was reversed by transfection with the miR-329-3p mimic. The overexpression of SNHG1 or knockdown of miR-329-3p inhibited OGD-induced BV-2 cell activation. In conclusion, the results of the present study suggested that SNHG1 may reduce microglial cell activity by regulating the expression of miR-329-3p, indicating its potential protective role in cerebral infarction.

SNHG5 protects chondrocytes in interleukin-1β-stimulated osteoarthritis via regulating miR-181a-5p/TGFBR3 axis.

Long noncoding RNAs (lncRNAs) have been considered as important modulators in the development of osteoarthritis. The present study investigates whether there is a link between lncRNA small nucleolar RNA host gene 5 (SNHG5) and osteoarthritis pathogenesis, and the underlying molecular mechanism. To establish an in vitro model of osteoarthritis, interleukin 1β (IL-1β) was used to treat chondrocytes (C20/A4 cells) for mimicking the inflammatory condition in osteoarthritis pathogenesis. SNHG5 and miR-181a-5p expression levels were then detected in cartilage tissues of osteoarthritis patients and C20/A4 cells by quantitative polymerase chain reaction (qPCR). Cell counting kit-8and 5-ethynyl-2'-deoxyuridine assays were applied for detecting the viability of chondrocytes, and the apoptosis of chondrocytes was examined through caspase-3 activity assay and flow cytometry analysis. Western blot and qPCR were employed for determining the expression levels of TGFBR3, ADAMTS5, and MMP-13. The regulatory relationships among SNHG5, miR-181a-5p, and TGFBR3 were verified by RNA immunoprecipitation and dual-luciferase reporter assays. The expression levels of SNHG5 and TGFBR3 were markedly decreased, and miR-181a-5p expression was enhanced in osteoarthritis tissues and chondrocytes treated with IL-1β. SNHG5 knockdown inhibited the viability of chondrocytes, induced apoptosis, and promoted the expression levels of ADAMTS5 and MMP-13. Conversely, SNHG5 overexpression could counteract the effects of IL-1β, increase the viability of chondrocytes and suppress apoptosis. Mechanically, SNHG5 positively regulated TGFBR3 expression via sponging miR-181a-5p. Moreover, miR-181a-5p overexpression and TGFBR3 knockdown counteracted the effects of SNHG5 on chondrocytes. SNHG5 can probably protect chondrocytes from the inflammatory response and reduce the degradation of the extracellular matrix via modulating the miR-181a-5p/TGFBR3 axis.

LncRNA SNHG22 sponges miR‑128‑3p to promote the progression of colorectal cancer by upregulating E2F3.

The long non-coding RNA (lncRNA) small nucleolar RNA host gene 22 (SNHG22) has been reported as a crucial regulator in several types of human cancer. The present study evaluated the function and mechanism of SNHG22 in colorectal cancer (CRC) progression. SNHG22 expression was detected in colorectal adenoma, CRC tumor tissues (TTs) and adjacent non-cancerous tissues (ANTs) using reverse transcription-quantitative PCR (RT-qPCR). The biological behaviors of SNHG22 in CRC cell lines were explored in vitro using Cell Counting Kit-8, flow cytometry, wound scratch assay and Transwell assay, and in vivo using a nude mouse xenograft model. The interaction between SNHG22 and microRNA-128-3p (miR-128-3p), and the target genes of miR-128-3p were explored using online tools, RT-qPCR, western blotting and a dual-luciferase reporter assay. The present study revealed that SNHG22 expression was most highly expressed in TTs followed by adenoma tissues and ANTs. In addition, high SNHG22 expression levels were significantly associated with advanced clinicopathological factors and worse survival in patients with CRC. SNHG22 knockdown markedly inhibited CRC cell proliferation, apoptosis resistance, migration and invasion in vitro, and hindered tumor growth in vivo. The mechanistic study revealed that SNHG22 bound to miR-128-3p and attenuated its inhibitory effects on E2F transcription factor 3 (E2F3) expression levels and activity. Rescue experiments demonstrated that inhibiting miR-128-3p or upregulating E2F3 offset the effects of SNHG22 knockdown on CRC cells. The present findings support the existence of an interactive regulatory network involving SNHG22, miR-128-3p and E2F3 in CRC cell lines, indicating that the SNHG22/miR-128-3p/E2F3 axis may be considered a novel diagnostic and therapeutic target in CRC.

Long non-coding RNA SNHG8 enhances triple-negative breast cancer cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis

BackgroundGrowing evidence has demonstrated that long non-coding RNAs (lncRNAs) can function as modulators in the development of triple-negative breast cancer (TNBC). However, the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in TNBC remains unclear. Therefore, our study aimed at investigating the role of SNHG8 in the proliferation and migration of TNBC cells.MethodsSNHG8 expression was evaluated using RT-qPCR assay. Cell proliferation and migration were assessed by EdU, colony formation and Transwell assays. The levels of proteins related to EMT process were examined by western blot assay. The interaction among SNHG8, miR-335-5p and pygopus family PHD finger 2 (PYGO2) was detected by RIP assay, RNA pull down assay and luciferase reporter assay.ResultsSNHG8 expression was significantly up-regulated in TNBC cells. SNHG8 silencing obviously inhibited TNBC cell proliferation, migration and EMT process. Moreover, SNHG8 acted as a sponge to sequester miR-335-5p in TNBC cells. Besides, PYGO2 was proven as a target gene of miR-335-5p, and SNHG8 promoted TNBC cell proliferation, migration and EMT process through regulating miR-335-5p and PYGO2.ConclusionsTotally, our study indicated that SNHG8 promoted TNBC cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis.

LncRNA SNHG7 Serves as a Potential Biomarker on the Prognosis of Human Solid Tumors: A Meta-Analysis.

Emerging studies on the predictive value of Small Nucleolar RNA Host Gene 7 (SNHG7) in human neoplasms give evidence of the association of SNHG7 with the human tumor. However, whether SNHG7 can be utilized as a biomarker for carcinoma is still unknown. Therefore, this meta-analysis is aimed to assess the possibility of SNHG7 serving as a tumor biomarker. 11 studies involving 814 cancer patients were retrieved from several databases, including PubMed, Embase, the Cochrane Library, and Web of Science from 1950 to Dec 27, 2019. Data on patient survival and several clinicopathological features were extracted and analyzed. Evident association between SNHG7 expression and poor Overall Survival (OS) was demonstrated (HR=1.84, 95% CI: 1.42-2.37) and high SNHG7 level was markedly correlated with tumor size (OR=2.01, 95% CI: 1.27-3.19), advanced clinical grade (III/IV) (OR=3.90, 95% CI: 2.63-5.80), Lymphatic Metastasis (LM) (OR=4.53, 95% CI: 2.71-7.55), and Distant Metastasis (DM) (OR=3.52, 95% CI: 2.58-4.80), except age and gender. Subgroup analysis showed that the predictive value of SNHG7 was consistent regardless of follow-up months, tumor location and sample size. Additionally, data from the R2 database also confirmed this association (p < 0.05). Publication bias was evaluated using Begg's and Egger's test. SNHG7 could serve for a promising biomarker to predict prognosis, progression and metastasis of human solid cancer.

Long Noncoding RNA Small Nucleolar RNA Host Gene 6 Promotes Cell Proliferation, Migration and Invasion in Melanoma by Sponging miR-944

Long noncoding RNA small nucleolar RNA host gene 6 (SNHG6) has been reported to be a tumor promoter in various human cancers. Nevertheless, the detailed functions and clinical value of SNHG6 in melanoma remain elusive. The study aimed to investigate the role and potential mechanism of SNHG6 in melanoma metastasis. Quantitative real-time PCR (qRT-PCR) was used to detect the expressions of SNHG6 and miR-944 in melanoma cells. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay, and cell migration and invasion were measured by wound healing assay and cell invasion assay, respectively. In addition, dual luciferase reporter assay was performed to verify the interaction between SNHG6 and miR-944. The protein expressions of PI3K/Akt pathway were evaluated by western blot assay. The results revealed that SNHG6 expression was significantly increased in melanoma cells. Knockdown of SNHG6 suppressed cell proliferation, migration and invasion in A375 cells. Moreover, miR-944 was identified as a direct target of SNHG6 in melanoma. miR-944 was downregulated in melanoma cells, while SNHG6 silencing improved miR-944 level in A375 cells. Rescue experiments demonstrated that miR-944 overexpression reversed the effects of SNHG6 on A375 cell proliferation, migration and invasion. Altogether, SNHG6 exerted oncogenic effects in melanoma cells, providing a novel promising target for the treatment of melanoma.

LncRNA SNHG12 regulates ox-LDL-induced endothelial cell injury by the miR-218-5p/IGF2 axis in atherosclerosis

ABSTRACT Atherosclerosis (AS) is a cardiovascular disorder accompanied by endothelial dysfunction. Extensive evidence demonstrates the regulatory functions of long noncoding RNAs (lncRNAs) in cardiovascular disease, including AS. Here, the function of lncRNA small nucleolar RNA host gene 12 (SNHG12) in AS progression was investigated. A cell model of AS was established in human umbilical endothelial cells (HUVECs) using oxidative low-density lipoprotein (ox-LDL). CCK-8, flow cytometry, TUNEL, ELISA, and western blotting analyses were performed. Apolipoprotein E-deficient (apoE−/−) mice fed a Western diet were used as in vivo models of AS. RT-qPCR determined the levels of SNHG12, microRNA-218-5p (miR-218-5p) and insulin-like growth factor-II (IGF2). The molecular mechanisms were investigated using luciferase reporter and RNA pull-down assays. We found that SNHG12 and IGF2 expression levels were high and miR-218-5p expression levels were low in AS patients and ox-LDL-treated HUVECs. SNHG12 depletion attenuated ox-LDL-induced injury in HUVECs, whereas miR-218-5p suppression partially abated this effect. Moreover, IGF2 overexpression prevented the alleviative role of miR-218-5p in ox-LDL-treated HUVECs. SNHG12 upregulated IGF2 expression by sponging miR-218-5p. More importantly, SNHG12 increased proinflammatory cytokine production and augmented atherosclerotic lesions in vivo. Overall, SNHG12 promotes the development of AS by the miR-218-5p/IGF2 axis.

LncRNA SNHG11 facilitates prostate cancer progression through the upregulation of IGF‑1R expression and by sponging miR‑184.

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) has been shown to play an important role in the development and progression of numerous types of cancer. However, to the best of our knowledge, the role of SNHG11 in prostate cancer (PCa) development and metastasis remains unclear. Thus, the aim of the present study was to investigate the functional role and molecular mechanisms of SNHG11 in PCa progression. It was revealed that the SNHG11 expression levels were significantly upregulated in PCa tissues, in comparison with those in adjacent normal tissues. Functionally, SNHG11 knockdown significantly suppressed PCa cell proliferation, migration, invasion and metastasis in vitro and in vivo. Furthermore, SNHG11 was found to positively regulate insulin-like growth factor 1 receptor (IGF-1R) expression by sponging microRNA (miRNA/miR)-184 in PCa cells. The results of rescue experiments demonstrated that IGF-1R overexpression reversed the suppressive effects of SNHG11 knockdown on the proliferation, migration and invasion of PCa cells. On the whole, the findings of the present study suggest that SNHG11 expression is upregulated in PCa and that it facilitates PCa progression, at least in part, via the modulation of the miR-184/IGF-1R signaling axis.

A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling.

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

ZIC2 upregulates lncRNA SNHG12 expression to promote endometrial cancer cell proliferation and migration by activating the Notch signaling pathway.

It was previously reported that long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) promoted the proliferation, invasion and migration of endometrial cancer (EC) cells; however, the upstream underlying mechanism remains unclear. The present study aimed to determine the possible underlying mechanism of SNHG12 regulating EC. The Encyclopedia of RNA Interactomes database was used to analyze whether SNHG12 could bind to Zic family member 2 (ZIC2) and the expression levels of ZIC2 in patients with EC. ZIC2 expression levels in EC cell lines were analyzed using western blotting and reverse transcription-quantitative PCR. RL95-2 cells were subsequently transfected with short hairpin RNA targeting ZIC2, or ZIC2 or SNHG12 overexpression plasmids. Cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8, colony formation, wound healing and Transwell assays, respectively. The binding between ZIC2 and SHNG12 was verified using dual luciferase reporter and chromatin immunoprecipitation assays. The results of the present study revealed that the expression levels of ZIC2 were upregulated in the tissues of patients with EC and EC cell lines. ZIC2 knockdown inhibited RL95-2 cell proliferation, migration and invasion. The protein expression levels of Ki67, proliferating cell nuclear antigen, MMP2 and MMP9 were also downregulated following the knockdown of ZIC2. ZIC2 was predicted to bind to SNHG12 and positively regulate SNHG12 expression. Further experiments demonstrated that the effects of the knockdown of ZIC2 on RL95-2 cells were partially reversed by SNHG12 overexpression. In addition, ZIC2 knockdown inhibited Notch signaling activation, while SNHG12 overexpression reversed this effect. In conclusion, the findings of the present study indicated that ZIC2 may upregulate SNHG12 expression to promote EC cell proliferation and migration by activating the Notch signaling pathway.

Downregulation of lncRNA SNHG14 alleviates neurons injury by modulating the miR-181c-5p/BMF axis in ischemic stroke

PurposeOur study aims to explore the role and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in brain injury caused by ischemic stroke (IS). MethodsMiddle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation (OGD)-induced primary cortical neurons were used to construct in vitro and in vivo models of IS, respectively. Relative SNHG14, miR-181c-5p and Bcl-2-modifying factor (BMF) expression levels were detected by quantitative real-time PCR. MTT assay, EdU staining and flow cytometry were used to measure cell proliferation and apoptosis. The protein levels of apoptosis marker and BMF were determined using western blot analysis. ELISA assay was performed to assess cell inflammatory response and injury. ResultsSNHG14 was upregulated and miR-181c-5p was downregulated in MCAO model and OGD-induced primary cortical neurons. Silencing of SNHG14 markedly promoted proliferation, restrained apoptosis and inflammatory response in OGD-induced primary cortical neurons to alleviate neurons injury. In terms of mechanism, miR-181c-5p could be sponged by SNHG14, and its inhibitor reversed the inhibition effect of SNHG14 silencing on OGD-induced neurons injury. Also, BMF was a target of miR-181c-5p, and its overexpression could reverse the suppressive effect of miR-181c-5p on OGD-induced neurons injury. Our data uncovered that BMF expression was positively regulated by SNHG14 and negatively regulated by miR-181c-5p. ConclusionOur results indicated that SNHG14 promoted neurons injury through regulating miR-181c-5p/BMF axis, suggesting that SNHG14 might be a potential target to alleviate IS-induced brain injury.

Expression and Regulatory Network Analysis of Function of Small Nucleolar RNA Host Gene 4 in Hepatocellular Carcinoma.

Background and AimsLong non-coding RNA small nucleolar RNA host genes (SNHGs) play a critical role in the occurrence and development of tumors. In this study, we aimed to investigate the role of SNHG4 in hepatocellular carcinoma (HCC) and its underlining mechanism.MethodsDatasets were acquired from The Cancer Genome Atlas (TCGA) database. lncLocator 2.0 was used to identify the distribution of SNHG4 in HCC cells. Gene expression, Kaplan-Meier survival, microRNA and transcription factor target analyses were performed with the University of Alabama Cancer (UALCAN) Database, Kaplan-Meier Plotter, LinkedOmics, WebGestalt and gene set enrichment analysis, respectively. Gene Ontology and pathway enrichment analyses and assessment of RNA binding proteins were performed by R software, circlncRNAnet and Encyclopedia of RNA Interactomes (ENCORI). In addition, CirclncRNAnet and ENCORI were used to find the correlation between SNHG4 and important proteins, while the prognostic value was assessed with the Human Protein Atlas database and Kaplan-Meier Plotter.ResultsExpression of SNHG4 in HCC is higher in HCC tissue than in normal healthy liver tissues and is mainly distributed in the nucleus. SNHG4 positively correlated with poor prognosis (p<0.01 for overall survival and recurrence-free survival). Functional enrichment analysis revealed SNHG4 involvement with regulation of ribosomal RNA synthesis and the RNA processing and surveillance pathway. SNHG4 is closely associated with miR-154 and miR-206, transcription factor target E2F family and the signaling pathway for MAPK/ERK and mTOR. U2 auxiliary factor 2 (U2AF2) showed strong correlation with SNHG4, while low-expression of U2AF2 showed good prognosis.ConclusionsBased on our findings, we infer SNHG4 may play a role in the formation of HCC via regulation of tumor-related pathways.

Long non-coding RNA SNHG16 regulates E2F1 expression by sponging miR-20a-5p and aggravating proliferative diabetic retinopathy.

Long non-coding RNAs (lncRNAs) were reported to be related to microvascular dysfunction in diabetic retinopathy (DR), but the potential mechanism remains unknown. This study was designed to elucidate the effects of lncRNA small nucleolar RNA host gene 1 (SNHG16) in proliferative DR progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the levels of SNHG16 and miR-20a-5p from peripheral blood samples of different participants. Pearson's correlation analysis was applied to the plasma data to detect correlations between SNHG16 and miR-20a-5p. Finally, the interactions of miR-20a-5p and SNHG16 or E2F1 were assessed by luciferase reporter assays. SNHG16 and E2F1 were increased and miR-20a-5p was decreased in proliferative DR both in vivo and in vitro when compared with control or non-proliferative DR. E2F1 was identified as the target of miR-20a-5p. The miR-20a-5p interacted with SNHG16 and E2F1 and was controlled by SNHG16. The regulation of SNHG16 on E2F1 was mediated by miR-20a-5p. Cells transfected with SNHG16 overexpression plasmid markedly increased cell apoptosis and vessel-like formation, whereas the miR-20a-5p mimic partially reversed these effects. Transfection with gene silencing E2F1 plasmid rescued SNHG16 overexpression-aggravated proliferative DR. This study indicated that SNHG16 regulated E2F1 expression by sponging miR-20a-5p and aggravating proliferative DR.

LncRNA SNHG3 Promotes Gastric Cancer Cells Proliferation, Migration, and Invasion by Targeting miR-326.

The function and possible mechanism of lncRNA Small Nucleolar RNA Host Gene 3 (SNHG3) in GC have not been fully studied. The aim of our study was to investigate the role of SNHG3 in the proliferation, migration, and invasion of GC cell lines. The expressions of SNHG3, miR-326, and TWIST in GC9811-P GC cell lines were detected by RT-qPCR. Western blotting was performed to detect the protein levels of TWIST and EMT-related genes. Luciferase reporter gene analysis and RNA immunoprecipitation (RIP) analysis confirmed the interaction between lncRNA SNHG3, miR-326, and TWIST. CCK-8 and Transwell assays were performed to detect cell proliferation, invasion, and migration abilities. The results showed that lncRNA SNHG3 and TWIST were highly expressed in GC cell lines, while miR-326 was expressed to a low degree. Moreover, lncRNA SNHG3 knockdown or miR-326 overexpression significantly inhibited cell proliferation, migration, and invasion of GC cell lines. In addition, TWIST overexpression can reverse the inhibition of lncRNA SNHG3 knockdown or miR-326 overexpression on cell proliferation, migration, and invasion. In conclusion, lncRNA SNHG3 may promote GC progression through the miR-326/TWIST axis, which may provide a new diagnostic and prognostic biomarker for GC.

SNHG17 Serves as an Oncogenic lncRNA by Regulating the miR-361-3p/STC2 Axis in Rectal Cancer

Long noncoding RNA (lncRNA) have been reported to be crucial regulators for carcinogenesis, including rectal cancer. This work aimed to explore the roles and associated mechanisms of small nucleolar RNA host gene 17 (SNHG17) in rectal cancer. A quantitative real-time polymerase chain reaction was performed to measure the expression level of SNHG17 in rectal cancer tissues and cells. Cell counting kit-8 (CCK-8) assay and flow cytometry assay were conducted to measure the biological roles of SNHG17 in rectal cancer. In addition, luciferase activity reporter assay, RNA immunoprecipitation (RIP) assay, and rescue experiments were conducted to explore the mechanisms of SNHG17 in rectal cancer. The upregulation status of SNHG17 was identified in rectal cancer tissues and cells. Functionally, knockdown the expression of SNHG17 inhibits rectal cancer cell proliferation via stimulating cell apoptosis. In vivo assay showed that the knockdown of SNHG17 inhibits tumor growth. Furthermore, we showed that microRNA-361-3p (miR-361-3p) has decreased expression in tumor tissues and cells, and SNHG17 functions as a sponge for miR-361-3p. The upregulation status of stanniocalcin 2 (STC2) was also found in rectal cancer, and the knockdown of STC2 hinders cancer progression. In conclusion, lncRNA SNHG17 functions as an oncogenic lncRNA in rectal cancer by regulating the miR-361-3p/STC2 axis.