Small Nucleolar RNA Host Gene 1 Expression Research Articles

Gastric cancer cell-derived extracellular vesicles elevate E2F7 expression and activate the MAPK/ERK signaling to promote peritoneal metastasis through the delivery of SNHG12

Cancer cell-derived extracellular vesicles (EVs) have extensive application in the formation of their environment, including metastasis. This study explored the ability of gastric cancer (GC) cell-derived EVs-mediated microRNA-129-5p/E2F transcription factor 7/mitogen-activated protein kinase/extracellular regulated protein kinase (miR-129-5p/E2F7/MAPK/ERK) axis to affect the peritoneal metastasis of GC by delivering lncRNA small nucleolar RNA host gene 12 (SNHG12). EV-derived lncRNA and SNHG12/miR-129-5p/E2F7 network were determined by bioinformatics analysis. The regulatory relationship among SNHG12, miR-129-5p, and E2F7 was verified using a combination of dual-luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down assays. The SNHG12, miR-129-5p, and E2F7 expression was measured by RT-qPCR. After GC cell-derived EVs were isolated and co-cultured with human peritoneal mesothelial cells (HPMCs), the uptake of EVs by HPMCs was observed under laser scanning confocal microscopy. Cell viability and apoptosis were examined using cell counting kit-8 and flow cytometry, respectively. Western blot analysis was performed to measure the mesothelial–mesenchymal transition (MMT)-related protein expression. The pathological and morphological characteristics of metastatic tumors in nude mice were observed by hematoxylin–eosin staining. A high SNHG12 expression was correlated with the poor prognosis of patients with GC. GC-derived EVs led to increased HPMC apoptosis and MMT by transferring SNHG12, whereas the knockdown of SNHG12 annulled the aforementioned results. SNHG12 sponged miR-129-5p to boost E2F7 expression and activate the MAPK/ERK signaling, thus inducing HPMC apoptosis and MMT. In vivo experiments further verified that EVs derived from GC cells promoted peritoneal metastasis in nude mice. GC cell-derived EVs elevated the E2F7 expression and activated the MAPK/ERK signaling to promote peritoneal metastasis through the delivery of SNHG12.

Long non-coding RNA SNHG5 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-212-3p/GDF5/SMAD pathway

BackgroundThe treatment of bone loss has posed a challenge to clinicians for decades. Thus, it is of great significance to identify more effective methods for bone regeneration. However, the role and mechanisms of long non-coding RNA small nucleolar RNA host gene 5 (SNHG5) during osteogenic differentiation remain unclear.MethodsWe investigated the function of SNHG5, Yin Yang 1 (YY1), miR-212-3p and growth differentiation factor 5 (GDF5) in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and in vivo. Molecular mechanisms were clarified by chromatin immunoprecipitation assay and dual luciferase reporter assay.ResultsWe found SNHG5 expression was upregulated during osteogenesis of hBMSCs. Knockdown of SNHG5 in hBMSCs inhibited osteogenic differentiation while overexpression of SNHG5 promoted osteogenesis. Moreover, YY1 transcription factor directly bound to the promoter region of SNHG5 and regulated SNHG5 expression to promote osteogenesis. Dual luciferase reporter assay confirmed that SNHG5 acted as a miR-212-3p sponge and miR-212-3p directly targeted GDF5 and further activated Smad1/5/8 phosphorylation. miR-212-3p inhibited osteogenic differentiation, while GDF5 promoted osteogenic differentiation of hBMSCs. In addition, calvarial defect experiments showed knockdown of SNHG5 and GDF5 inhibited new bone formation in vivo.ConclusionOur results demonstrated that the novel pathway YY1/SNHG5/miR-212-3p/GDF5/Smad regulates osteogenic differentiation of hBMSCs and may serve as a potential target for the treatment of bone loss.

Role and mechanism of the lncRNA SNHG1/miR‑450b‑5p/IGF1 axis in the regulation of myocardial ischemia reperfusion injury.

The increasing rates of morbidity and mortality caused by ischemic heart disease pose a serious threat to human health. Long non-coding (lnc)RNA small nucleolar RNA host gene 1 (SNHG1) has a protective effect on the myocardium. In the present study, the role of lncRNA SNHG1 in myocardial ischemia reperfusion injury (MIRI) and the underlying mechanisms were investigated. After hypoxia/reoxygenation (H/R) induction, the expression levels of lncRNA SNHG1 were detected using reverse transcription-quantitative PCR. After lncRNA SNHG1 overexpression via cell transfection, cell viability was detected using an MTT assay, apoptotic rates were detected using TUNEL staining, apoptosis-related protein expression levels were detected using western blotting and respective kits were used to measure the oxidative stress levels. The Encyclopedia of RNA Interactomes database predicted the presence of binding sites between lncRNA SNHG1 and microRNA (miR)-450b-5p, and between miR-450b-5p and insulin-like growth factor 1 (IGF1). These interactions were then verified using luciferase reporter assays. Subsequently, the regulatory mechanism underlying the lncRNA SNHG1/miR-450b-5p/IGF1 axis in MIRI was investigated by overexpressing miR-450b-5p and knocking down IGF1 expression in H/R-induced cells. Finally, the expression of PI3K/Akt signaling pathway-related proteins was detected using western blotting. lncRNA SNHG1 expression was significantly downregulated in H/R-induced AC16 cells. lncRNA SNHG1 overexpression significantly inhibited apoptosis and decreased oxidative stress levels in H/R-induced AC16 cells, which was mediated via regulation of the miR-450b-5p/IGF1 axis and activation of the PI3K/Akt signaling pathway. Therefore, the present study suggested that activation of the PI3K/Akt signaling pathway via the lncRNA SNHG1/miR-450b-5p/IGF1 axis inhibited the apoptosis and oxidative stress levels of H/R-induced AC16 cells.

LncRNA small nucleolar RNA host gene 5 inhibits trophoblast autophagy in preeclampsia by targeting microRNA-31-5p and promoting the transcription of secreted protein acidic and rich in cysteine

ABSTRACT Preeclampsia (PE) is a pregnancy-related complication. Dysregulation of long non-coding RNAs (lncRNAs) contributes to the pathogenesis of PE. The current study sought to investigate the effect of lncRNA small nucleolar RNA host gene 5 (SNHG5) on trophoblast autophagy in PE. A PE mouse model was established, followed by detection of parameters such as blood pressure, proteinuria, triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein, observation of alterations of mouse placenta and kidney, and detection of B-cell chronic lymphocytic leukemia/lymphoma-2, Bcl-2-associated X protein, and SNHG5 expression patterns. The expressions of LC3, Beclin-1, and p62 in the placenta of PE mice were detected. Moreover, the SNHG5 expression was downregulated in the established HTR-8/SVneo trophoblast model, followed by evaluation of cell proliferation, apoptosis, and autophagy. After combination treatment with 3-MA (an autophagy inhibitor) and si-SNHG5, the behaviors of HTR-8/SVneo cells were observed. The binding relations between SNHG5 and miR-31-5p, and miR-31-5p and SPARC were verified. The expressions of miR-31-5p and SPARC in the placenta of mice and trophoblasts were determined. Our results demonstrated a poor expression of lncRNA SNHG5 in PE mice. SNHG5 overexpression reduced the PE phenotype and tissue damage in mice. SNHG5 silencing reduced the proliferation, migration, and invasion of trophoblasts, but elevated apoptosis and autophagy. SNHG5 sponged miR-31-5p to promote SPARC transcription. Additionally, miR-31-5p knockdown or 3-MA treatment reverted the stimulative effect of SNHG5 silencing on trophoblast autophagy. Collectively, our study demonstrated that lncRNA SNHG5 alleviated the PE phenotype and inhibited trophoblast autophagy by sponging miR-31-5p and promoting SPARC transcription.

LncRNA SNHG1 Delayed Fracture Healing via Modulating miR-181a-5p/PTEN Axis

Background:The purpose of this study was to investigate the role of Long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in delayed healing of tibial fractures and its potential regulatory mechanisms. Methods: 51 patients with normal healing of tibial fractures and 46 patients with delayed healing of tibial fractures were enrolled. RT-qPCR was performed to analyze SNHG1, microRNA (miRNA)-181a-5p, and PTEN levels. ROC curves were used to detect the predictive value of SNHG1 for delayed healing in fracture patients. Subsequently, the regulation of osteogenic markers by SNHG1 and miR-181a-5p was analyzed in MC3T3-E1. Cell proliferation and apoptosis were quantified by CCK-8 and flow cytometry. The binding between SNHG1/miR-181a-5p/PTEN was detected by dual-luciferase reporter gene assay. Results: Serum SNHG1 and PTEN expression were upregulated and miR-181a-5p expression was downregulated in patients with delayed fracture healing. SNHG1 decreased the level of osteogenic markers in MC3T3-E1, inhibited the proliferation, and stimulated apoptosis of MC3T3-E1 (P < 0.05). SNHG1 acted as a sponge for miR-181a-5p, and elevation of miR-181a-5p abolished the inhibition of osteogenic differentiation and promotion of apoptosis by SNHG1 (P < 0.05). PTEN was identified as a target of miR-181a-5p and involved in this regulatory process. Finally, elevated SNHG1 was a feasible predictive biomarker in patients with delayed fracture healing. Conclusion: The current study revealed that SNHG1/miR-181a-5p/PTEN axis inhibited osteoblast differentiation and proliferation and promoted apoptosis, thus leading to the inhibition of tibial fracture healing. Our findings contribute to the understanding of the mechanisms underlying delayed tibial fracture healing.

Potential diagnostic and prognostic value of the long non-coding RNA SNHG3 in human cancers: A systematic review and meta-analysis.

Small nucleolar RNA host gene 3 (SNHG3), as a novel long non-coding RNA (lncRNA) participates in the oncogenic processes of various cancers. We combined a systematic review and a meta-analysis to assess the potential role of SNHG3 as a pan-cancer marker for cancer diagnosis and prognosis. Our study comprehensively searched for SNHG3 expression profiling studies from PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, Google Scholar, and The Cancer Genome Atlas (TCGA). The diagnostic capacity of SNHG3 for all cancers in TCGA database was evaluated from the perspective of pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve. Also, this research studied the correlation of SNHG3 expression and the overall survival to access its prognostic value. A sum total of 11,888 cancer patients and 730 controls from 44 eligible studies were enrolled in this integrated analysis. In TCGA database, SNHG3 was significantly upregulated in most types of cancers (16/33, 48%). The pooled sensitivity, specificity, and DOR with 95% CIs was 0.72 (95% CI: 0.60-0.82), 0.87 (95% CI: 0.84-0.90), and 18 (95% CI: 11-30), respectively. Similarly, the AUC of the sROC curve was 0.89 (95% CI: 0.86-0.92), indicating SNHG3 was highly conserved as a diagnosis biomarker. Additionally, SNHG3 overexpression significantly deteriorated the overall survival of cancer patients (pooled HR = 1.28, 95% CI:1.11-1.48; P < 0.05). These findings suggest that the lncRNA SNHG3 could serve as a promising diagnostic and prognostic biomarker.

LncRNA SNHG12 promotes the malignant progression of melanoma by targeting miR-199b.

BackgroundMelanoma is a type of tumor caused by the malignant transformation of melanocytes, and has a high degree of malignancy. Small nucleolar RNA host gene 12 (SNHG12) plays an important role in a variety of cancers, but its role in melanoma and its mechanisms are still unclear. In this study, we measured the expression of SNHG12 and explored the molecular mechanisms involved in melanoma.MethodsWe detected the expression level of SNHG12 in melanoma cell lines, and explored the effect of SNHG12 on the proliferation, migration, and invasion of melanoma cells in vitro. Mechanistic studies explored the regulation of downstream genes by SNHG12.ResultsOverexpression of SNHG12 was found in melanoma cell lines, and SNHG12 promoted the proliferation, migration, and invasion of melanoma cells. MiR-199b is a target gene of SNHG12, which was expressed at low levels in melanoma cell lines, and SNHG12 regulated melanoma cell proliferation, migration, and invasion through miR-199b. We also revealed that SNHG12 promoted the expression of the target genes of miR-199b, namely ETS1, PXN, JAG1, and DDR1.ConclusionsSNHG12 is highly expressed in melanoma, and promotes the expression of ETS1, PXN, JAG1, and DDR1 through targeted regulation of miR-199b, thereby promoting the proliferation, migration, and invasion of melanoma cells.

Exosome-mediated transfer of SNHG7 enhances docetaxel resistance in lung adenocarcinoma.

Long noncoding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been widely reported in various cancers, including lung adenocarcinoma (LUAD). However, it is largely unknown whether SNHG7 is involved in docetaxel resistance of LUAD. In the current study, we identified the high expression of SNHG7 in docetaxel-resistant cells. Through functional assays, we determined that silencing of SNHG7 decreased IC50 value of LUAD cells to docetaxel and suppressed proliferation and autophagy in LUAD cells, and reversed M2 polarization in macrophages. Mechanistically, we uncovered that SNHG7 promoted autophagy via recruiting human antigen R (HuR) to stabilize autophagy-related genes autophagy related 5 (ATG5) and autophagy related 12 (ATG12). Moreover, exosomal SNHG7 was transmitted from docetaxel-resistant LUAD cells to parental LUAD cells and thus facilitated docetaxel resistance. Additionally, exosomal SNHG7 activated the phosphatidylinositol 3-kinase (PI3K)/AKT pathway to promote M2 polarization in macrophages via recruiting cullin 4A (CUL4A) to induce ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Taken together, we concluded that exosomal SNHG7 enhances docetaxel resistance of LUAD cells through inducing autophagy and macrophage M2 polarization. All findings in the study suggested that SNHG7 may be a promising target for relieving docetaxel resistance in LUAD.

Oncogenic Roles of Small Nucleolar RNA Host Gene 7 (SNHG7) Long Noncoding RNA in Human Cancers and Potentials.

Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts characterized with more than 200 nucleotides of length. Unlike their names, some short open reading frames are recognized for them encoding small proteins. LncRNAs are found to play regulatory roles in essential cellular processes such as cell growth and apoptosis. Therefore, an increasing number of lncRNAs are identified with dysregulation in a wide variety of human cancers. SNHG7 is an lncRNA with upregulation in cancer cells and tissues. It is frequently reported with potency of promoting malignant cell behaviors in vitro and in vivo. Like oncogenic/tumor suppressor lncRNAs, SNHG7 is found to exert its tumorigenic functions through interaction with other biological substances. These include sponging target miRNAs (various numbers are identified), regulation of several signaling pathways, transcription factors, and effector proteins. Importantly, clinical studies demonstrate association between high SNHG7 expression and clinicopathological features in cancerous patients, worse prognosis, and enhanced chemoresistance. In this review, we summarize recent studies in three eras of cell, animal, and human experiments to bold the prognostic, diagnostic, and therapeutic potentials.

SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression

BackgroundAbnormal expression of long noncoding RNAs (lncRNAs) has been reported in the acute stage of acute ischemic stroke (AIS). This study aimed to explore differential lncRNA expression in the subpopulations of peripheral blood mononuclear cells (PBMCs) from AIS patients and further evaluate its underlying mechanisms in stroke-induced immunosuppression.MethodsWe reanalyzed lncRNA microarray data and investigated abnormally expressed lncRNAs in the subpopulations of PBMCs by magnetic cell sorting and real-time quantitative PCR. The potential mechanism of small nucleolar RNA host gene 15 (SNHG15) was explored through in vitro and in vivo approaches.ResultsThe stroke-induced SNHG15 acted as a checkpoint to inhibit peripheral inflammatory responses. Functional studies showed that SNHG15 promoted M2 macrophage polarization. Mechanistically, SNHG15 expression was dysregulated through the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) signaling pathway. SNHG15, localized in the cytoplasm, interfered with K63-linked ubiquitination of tumor necrosis factor receptor-associated factor 2 and thereby repressed the activation of mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and prevented the production of proinflammatory cytokines. Administration of an adenovirus targeting SNHG15 improved stroke-induced immunosuppression in mice.ConclusionsThis study identified SNHG15 as a negative regulator of inflammation in stroke-induced immunosuppression, suggesting it as a novel biomarker and therapeutic target in stroke-associated infection.Trial registration ClinicalTrials.gov NCT04175691. Registered November 25, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691.

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.

LncRNA SNHG6 knockdown inhibits cisplatin resistance and progression of gastric cancer through miR-1297/BCL-2 axis.

Cisplatin (DDP) resistance is a huge obstacle to gastric cancer (GC) treatment. Long non-coding RNAs (lncRNAs) have been manifested to exert pivotal functions in GC development. Herein, we aimed to explore the functional impact of lncRNA small nucleolar RNA host gene 6 (SNHG6) on DDP resistance and progression of GC. Quantitative real-time PCR (qRT-PCR) assay or Western blotting was performed to detect the expression of SNHG6, microRNA(miR)-1297, and epithelial–mesenchymal transition (EMT)-related factors and B-Cell Lymphoma 2 (Bcl-2) in DDP-resistant GC cells. Half inhibition concentration (IC50) to DDP, clonogenicity, apoptosis and invasion were examined via CCK-8 assay, colony formation assay, flow cytometry and Transwell assay, respectively. Target association between miR-1297 and SNHG6 or BCL-2 was demonstrated via dual-luciferase reporter assay or RIP assay. Xenograft models in nude mice were formed to investigate role of SNHG6 in vivo. We found that SNHG6 and BCL-2 were up-regulated, while miR-1297 expression was declined in GC tissues and DDP-resistant cells. Moreover, depletion of SNHG6 or gain of miR-1297 could repress DDP resistance, proliferation and metastasis of DDP-resistant cells, which was weakened by miR-1297 inhibition or BCL-2 overexpression. Besides, SNHG6 positively regulated BCL-2 expression by sponging miR-1297. Furthermore, SNHG6 knockdown repressed GC tumor growth in vivo. In a word, lncRNA SNHG6 knockdown had inhibitory effects on DDP resistance and progression of GC by sponging miR-1297, highlighting its potential in GC treatment.

Is Long Noncoding SNHG7 a Reliable Diagnostic Tool for Metastasis Diagnosis of Cancer: A Meta-Analysis.

Background: The small nucleolar RNA host gene 7 (SNHG7) has been suggested as a biomarker of metastatic cancer; however, its reliability is controversial. Therefore, the goal of this study was to conduct a meta-analysis to assess the reliability of SNHG7 as a comprehensive cancer metastasis diagnostic biomarker. Methods: A comprehensive literature search was conducted using PubMed, Cochrane Library, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) to identify articles which examined the role of SNHG7 in cancers. Random-effects models and fixed-effects models were conducted to estimate the pooled odds ratios (ORs) for the associations of SNHG7 with distant metastases and lymph node metastases. Hierarchical summary receiver operating characteristic (ROC) models were used to estimate the sensitivity and specificity of SNHG7 as a biomarker for cancer metastasis diagnoses. Results: Nineteen studies comprised 1491 patients were included in this meta-analysis. We found that both distant metastasis (OR = 4.19, 95% confidence interval [CI] = 2.93-5.99, I2 = 34%) and lymph node metastasis (OR = 3.07, 95% CI = 1.65-5.68, I2 = 79.03%) were significantly associated with a higher expression of SNHG7. We also showed a pooled sensitivity and specificity of 74% (95% CI = 66-82) and 57% (95% CI = 53-61) for distant metastasis; as well as 72% (95% CI = 63-80) and 54% (95% CI = 46-63) for lymph node metastasis, respectively. Conclusion: Our findings suggest that SNHG7 is a potential diagnostic biomarker for metastasis of cancer; however, its clinical application requires stronger evidence due to the low sensitivity and specificity. Further larger-scale studies from diverse settings and cancer types will be necessary to reveal novel insights into SNHG7 as a biomarker for cancer metastasis diagnoses.

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.

LncRNA SNHG20 promotes migration and invasion of ovarian cancer via modulating the microRNA-148a/ROCK1 axis

BackgroundOvarian cancer (OC) is characterized by early metastasis and poor prognosis, which threatens the health of women worldwide. Small nucleolar RNA host gene 20 (SNHG20), a long noncoding RNA (lncRNA), has been verified to be significantly up-regulated in several tumors, including OC. MicroRNA-148a (miR-148a)/rho-kinase1 (ROCK1) axis plays an important role in the modulation of tumor development. However, whether SNHG20 can regulate OC progression through miR-148a/ROCK1 axis remains unclear. Normal human ovarian epithelial cell line and four OC cell lines were adopted for in vitro experiments. Real-time PCR was performed to assess the levels of SNHG20 and miR-148a. OC cell proliferation, apoptosis, invasion and migration were detected using clone formation, flow cytometry, transwell, and wound healing assays, respectively. Tumor xenograft assay was applied to evaluate the effect of SNHG20 on tumor growth in vivo.ResultsSignificant higher expression of SNHG20 was observed in OC cell lines. SNHG20 markedly promoted the invasion, migration, proliferation and inhibited the apoptosis of OC cells. SNHG20 enhanced ROCK1 expression by sponging miR-148a, and the direct binding between SNHG20/ROCK1 and miR-148a was identified.ConclusionSNHG20 promoted invasion and migration of OC via targeting miR-148a/ROCK1 axis. The present research may provide a novel insight for the therapeutic strategies of OC.

Long noncoding RNA SNHG3 promotes malignant phenotypes in cervical cancer cells via association with YAP1

Long non-coding RNA (LncRNA) Small Nucleolar RNA Host Gene 3 (SNHG3) is involved in the occurrence and development of various cancers. However, the exact function and mechanism of SNHG3 in cervical cancer (CC) are still unclear. In this context, we identified a significant increase of SNHG3 expression in CC tissues. Upregulation of SNHG3 expression was associated with advanced FIGO stage and metastasis, and indicated poor overall survival of the CC patients. Functionally, SNHG3 enhanced the proliferation, migration and invasion of CC cells in vitro, and facilitated CC growth in vivo. Further investigation uncovered that SNHG3 interacted with oncoprotein YAP1, thus suppressing its degradation. Additionally, SNHG3 modulated the transcription of several target genes of YAP1. The oncogenic role of SNHG3 was partially attributable to YAP1. Taken together, our research revealed the prognostic and functional roles for SNHG3 in CC, suggesting that SNHG3 could serve as a biomarker for prognosis and a therapeutic target for CC.

LncRNA SNHG14 accelerates breast cancer progression through sponging miR-543 and regulating KLF7 expression.

Dysregulation of long non-coding RNAs (lncRNAs) is being found to have relevance to human cancers, including breast cancer (BC). The aim of this study was to further explore the functional role and molecular mechanisms of small nucleolar RNA host gene 14 (SNHG14) on BC progression. The expression levels of SNHG14, miR-543, and krüppel-like factor 7 (KLF7) mRNA were determined by quantitative real-time PCR. Western blot analysis was used to evaluate KLF7 protein level. Cell proliferation, apoptosis, and migration and invasion abilities were detected by Cell Counting kit-8 assay, flow cytometry, and transwell assay, respectively. The direct interactions between miR-543 and SNHG14 or KLF7 were confirmed using dual-luciferase reporter assays. Our data indicated that SNHG14 expression was increased in BC tissues and cells, and SNHG14 knockdown mitigated the proliferation, migration, and invasion and facilitated apoptosis of BC cells. SNHG14 directly interacted with miR-543. MiR-543 mediated the regulatory effects of SNHG14 silencing on BC cell behaviors. Moreover, KLF7 was a direct target of miR-543. Overexpressed miR-543-mediated anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis effects were mediated by KLF7. Furthermore, SNHG14 modulated KFL7 expression through acting as a competing endogenous RNA (ceRNA) of miR-543 in BC cells. Our study suggested that SNHG14 knockdown hindered BC progression in vitro at least partly through acting as a ceRNA of miR-543 and modulating KLF7 expression, providing evidence for SNHG14 as a potential target for BC therapy.

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.

LncRNA SNHG6 promotes hepatocellular carcinoma progression by interacting with HNRNPL/PTBP1 to facilitate SETD7/LZTFL1 mRNA destabilization.

The lncRNA SNHG6 (small nucleolar RNA host gene 6) plays vital roles in tumorigenesis and the progression of hepatocellular carcinoma (HCC). However, the regulatory mechanisms of SNHG6 are largely unknown. In this study, we identified, via quantitative proteomics, specific cytoskeleton-associated proteins and enzyme modulators to be potential targets of SNHG6. SNHG6 reduced the mRNA levels of lysine methyltransferase, SET domain containing 7 (SETD7) and leucine zipper transcription factor-like 1 (LZTFL1) by posttranscriptional destabilization. Silencing of SETD7 or LZTFL1 reversed the suppressive effects of SNHG6 knockdown on HCC progression. Heterogeneous nuclear ribonucleoprotein L (HNRNPL) and polypyrimidine tract binding protein 1 (PTBP1) were identified as SNHG6-interacting proteins that bind to SETD7 or LZTFL1 mRNA. Forced expression of SNHG6 led to HNRNPL being competitively adsorbed by SNHG6, thereby removing its stabilizing effect on SETD7. Concurrently, the functional SNHG6-PTBP1 complex facilitated the degradation of LZTFL1 mRNA in hepatoma cells. These results indicated that SNHG6 promotes HCC progression by functioning as a "decoy plus guide" for HNRNPL and PTBP1 to facilitate mRNA decay of SETD7 and LZTFL1, thereby serving as a novel therapeutic target for HCC.