Single-nucleus analysis reveals microenvironment-specific neuron and glial cell enrichment in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a complicated neurodegenerative disease. Neuron-glial cell interactions are an important but not fully understood process in the progression of AD. We used bioinformatic methods to analyze single-nucleus RNA sequencing (snRNA-seq) data to investigate the cellular and molecular biological processes of AD. METHOD: snRNA-seq data were downloaded from Gene Expression Omnibus (GEO) datasets and reprocessed to identify 240,804 single nuclei from healthy controls and patients with AD. The cellular composition of AD was further explored using Uniform Manifold Approximation and Projection (UMAP). Enrichment analysis for the functions of the DEGs was conducted and cell development trajectory analyses were used to reveal underlying cell fate decisions. iTALK was performed to identify ligand-receptor pairs among various cell types in the pathological ecological microenvironment of AD. RESULTS: Six cell types and multiple subclusters were identified based on the snRNA-seq data. A subcluster of neuron and glial cells co-expressing lncRNA-SNHG14, myocardin-related transcription factor A (MRTFA), and MRTFB was found to be more abundant in the AD group. This subcluster was enriched in mitogen-activated protein kinase (MAPK)-, immune-, and apoptosis-related pathways. Through molecular docking, we found that lncRNA-SNHG14 may bind MRTFA and MRTFB, resulting in an interaction between neurons and glial cells. CONCLUSIONS: The findings of this study describe a regulatory relationship between lncRNA-SNHG14, MRTFA, and MRTFB in the six main cell types of AD. This relationship may contribute to microenvironment remodeling in AD and provide a theoretical basis for a more in-depth analysis of AD.

LncRNA SNHG14/miR-497a-5p/BACE1 axis modulates obesity-induced adipocyte inflammation and endoplasmic reticulum stress.

Obesity is a metabolic disease with excess weight. LncRNA SNHG14 is abnormally expressed in numerous diseases. This research aimed to enucleate the lncRNA SNHG14 role in obesity. Adipocytes were treated with free fatty acid (FFA) to establish an in vitro model for obesity. Mice were fed a high-fat diet to construct an in vivo model. Gene levels were determined using quantitative real-time PCR (RT-PCR). The protein level was checked by western blot. The lncRNA SNHG14 role in obesity was assessed using western blot and enzyme-linked immunosorbent assay. The mechanism was estimated by Starbase, dual-luciferase reporter gene assay, and RNA pull-down. LncRNA SNHG14 function in obesity was estimated using mouse xenograft models, RT-PCR, western blot, and enzyme-linked immunosorbent assay. LncRNA SNHG14 and BACE1 levels were increased, but the miR-497a-5p level was decreased in FFA-induced adipocytes. Interference with lncRNA SNHG14 reduced endoplasmic reticulum (ER) stress-related molecules GRP78 and CHOP expressions in FFA-induced adipocytes, and decreased IL-1ß, IL-6, and TNF-α expressions, indicating that lncRNA SNHG14 knockdown mitigated FFA-induced ER stress and inflammation in adipocytes. Mechanistically, lncRNA SNHG14 combined with miR-497a-5p, and miR-497a-5p targeted BACE1. Meanwhile, lncRNA SNHG14 knockdown reduced levels of GRP78, CHOP, IL-1ß, IL-6, and TNF-α, while cotransfection with anti-miR-497a-5p or pcDNA-BACE1 abolished these trends. Rescue assays illustrated that lncRNA SNHG14 knockdown relieved FFA-induced adipocyte ER stress and inflammation through miR-497a-5p/BACE1. Meanwhile, lncRNA SNHG14 knockdown restrained adipose inflammation and ER stress caused by obesity in vivo. LncRNA SNHG14 mediated obesity-induced adipose inflammation and ER stress through miR-497a-5p/BACE1.

Dexmedetomidine inhibits microglial activation through SNHG14/HMGB1 pathway in spinal cord ischemia-reperfusion injury mice.

OBJECTIVE: Microglial activation is an essential pathological mechanism of spinal cord ischemia-reperfusion injury (SCIRI). Previous studies showed dexmedetomidine (DEX) could alleviate SCIRI while the mechanism was not clear. This study aims to investigate the role of DEX in microglial activation and clarify the underlying mechanism. METHODS: The motion function of mice was quantified using the Basso Mouse Scale for Locomotion. The expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) was determined by qRT-PCR. The expression of high-mobility group box 1 (HMGB1) was measured by western blot. The activation of microglia was evaluated by the expression of ED-1 and the levels of TNF-α and IL-6. The interplay between SNHG14 and HMGB1 was confirmed with RNA pull-down and RIP assay. The stability of HMGB1 was measured by ubiquitination assay and cycloheximide-chase assay. RESULTS: DEX inhibited microglial activation and down-regulated SNHG14 expression in SCIRI mice and oxygen and glucose deprivation/reoxygenation (OGD/R)-treated primary microglia. Functionally, SNHG14 overexpression reversed the inhibitory effect of DEX on OGD/R-induced microglial activation. Further investigation confirmed that SNHG14 bound to HMGB1, positively regulated HMGB1 expression by enhancing its stability. In addition, the silence of HMGB1 eliminated the pro-activation impact of SNHG14 overexpression on DEX-treated microglia under the OGD/R condition. Finally, in vivo experiments showed SNHG14 overexpression abrogated the therapeutic effect of DEX on SCIRI mice by up-regulating HMGB1. CONCLUSION: DEX accelerated HMGB1 degradation via down-regulating SNHG14, thus inhibiting microglial activation in SCIRI mice.

lncRNA SNHG14 involved in trophoblast cell proliferation, migration, invasion and epithelial-mesenchymal transition by targeting miR-330-5p in preeclampsia.

Preeclampsia (PE), a pregnancy-specific disease, has become one of the leading causes of maternal and neonatal morbidity and mortality. Pathogenesis of PE has still not been fully addressed and there is a great need to develop early diagnosis markers and effective therapy. This study aimed to determine if lncRNA SNHG14 has a protective effect on placental trophoblast and prevents PE. SNHG14 levels in the peripheral blood from patients with PE or from women with healthy pregnancies were detected using RT-qPCR. The relationship between SNHG14 and miR-330-5p was determined using a dual-luciferase reporter assay. In addition, cell proliferation and cell cycle were evaluated by performing CCK8 assays and flow-cytometric analysis, respectively. Wound-healing and transwell assays were performed to assess cell migration and invasion ability. lncRNA SNHG14 was downregulated in PE patients; it was involved in trophoblast proliferation and regulated cell proliferation during G1/S transition. In addition, lncRNA SNHG14 promoted migration, invasion and epithelial-mesenchymal transition (EMT) in HTR-8/SVneo cells. Luciferase reporter assay indicated that lncRNA SNHG14 served as a molecular sponge for miR-330-5p and negatively regulated miR-330-5p expression in PE. Furthermore, the effects of silenced SNHG14 on trophoblast proliferation, migration, invasion and EMT were reversed by addition of miR-330-5p inhibitor, suggesting that in PE lncRNA SNHG14 functions by competitively binding to miR-330-5p. Taken together, the current study demonstrated that in PE lncRNA SNHG14 is a vital regulator by binding to miR-330-5p. SNHG14 might serve as a therapeutic application in PE progression.

LncRNA SNHG14 regulates the DDP-resistance of non-small cell lung cancer cell through miR-133a/HOXB13 pathway.

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have been reported to be involved in regulating chemo-resistance of NSCLC, however, the role of lncRNA SNHG14 in the DDP-resistance of NSCLC remains unexplored. METHODS: Relative expression of SNHG14, HOXB13 and miR-133a in DDP-resistant A549 (A549/DDP) cell and its parental cell A549 were measured using qRT-PCR. Cell proliferation viability of indicated A549/DDP cell was estimated via CCK-8 and colony formation experiments. Cell cycle and apoptosis were analyzed through flow cytometry. Expression of apoptosis-related protein and HOXB13 were detected via western blot. The interaction among SNHG14, HOXB13 and miR-133a was predicted by bioinformatics and validated by dual-luciferase reporter assay. RESULTS: LncRNA SNHG14 and HOXB13 were upregulated while miR-133a was downregulated in A549/DDP cell line compared to A549 cell line. SNHG14 knockdown or miR-133a overexpression was demonstrated to increase the DDP-sensitivity of A549/DDP cells. SNHG14 was revealed to compete with HOXB13 for miR-133a binding in A549/DDP cells. Inhibition of miR-133a in A549 cells could reverse the promotive effects of SNHG14 knockdown on DDP-sensitivity, as well as the inhibitory effects on HOXB13 expression. HOXB13 overexpression was revealed to abolish the enhanced effects of miR-133a on the sensitivity of A549/DDP cell to DDP. CONCLUSION: Our findings demonstrated that SNHG14 was involved in the development of DDP-resistance of A549/DDP cells through miR-133a/HOXB13 axis, which may present a path to novel therapeutic stratagems for DDP resistance of NSCLC.

Values of LncRNA SNHG14 in the Differential Diagnosis and Prognosis Evaluation of Acute Ischemic Stroke.

The long non-coding RNA (LncRNA) SNHG14 has been investigated for its potential in acute ischemic stroke (AIS) and transient ischemic attack (TIA) diagnosis. Thirty-two healthy people, 85 patients with AIS, and 40 patients with TIA had their blood tested to determine SNHG14 mRNA transcript levels using quantitative real-time polymerase chain reaction (qRT-PCR). A stroke's severity was measured using the Stroke Severity Scale developed by the National Institutes of Health (NIHSS). After 30 days, individuals with AIS were evaluated for progress using a modified Rankin Scale (mRS). There was no significant difference in SNHG14 LncRNA levels between TIA patients and controls, despite the huge rise in AIS incidence (p > 0.05) (all p < 0.001). Compared to those who did well on the AIS test, those who performed poorly had substantially greater levels of SNHG14 LncRNA (mRS 0-1 points) (mRS 0-2). LncRNA SNHG14 had an AUC of 0.714 (80%, 61.18%) when used to identify AIS in TIA patients, and a comparable finding was seen when predicting a poor 30-day prognosis of AIS (73%, 66.67%). There are also graphical representations of the findings. Improvements in NIHSS and mRS scores were associated with increases in SNHG14 LncRNA mRNA levels in individuals diagnosed with AIS. It is critical that we focus entirely on this decision (all p < 0.05). Analysis of the long non-coding RNA known as SNHG14 in the patient's blood can be used to diagnose AIS, rule out TIA, forecast the intensity of the disease, and evaluate the prognosis. You can accomplish everything on that list simultaneously.

Inhibition of LncRNA SNHG14 protects chondrocyte from injury in osteoarthritis via sponging miR-137.

Long-chain noncoding small nucleolar RNA host gene 14 (LncRNA SNHG14) is highly expressed in various diseases and promotes diseases progression, but the role and mechanism of LncRNA SNHG14 on targeting miR-137 in promoting osteoarthritis (OA) chondrocyte injury remains unclear. To measure the expression of the LncRNAs SNHG14 and miR-137, cell survival, inflammatory response, chondrocyte apoptosis, and extracellular matrix (ECM) levels, we subjected human chondrocytes to a variety of lipopolysaccharide (LPS) concentrations. To measure the luciferase activity of SNHG14-WT and SNHG14-MUT transfected with miR-137 mimic or miR-NC mimic, luciferase reporter genes were utilized. The results showed that chondrocyte viability was significantly inhibited with LPS treatment and chondrocyte inflammatory response, apoptosis and extracellular matrix degradation were significantly increased. However, the above results were significantly reversed after LncRNA SNHG14 inhibition. The luciferase activity bound to miR-137 was decreased in SNHG14-WT group, but there was no change in SNHG14-mut group, which indicated that LncRNA SNHG14 inhibited miR-137 expression as a miRNA sponge. In conclusion, inhibition of LncRNA SNHG14 attenuates chondrocyte inflammatory response, apoptosis and extracellular matrix degradation by targeting miR-137 in LPS induced chondrocytes.

The role of lncRNA SNHG14 in gastric cancer: enhancing tumor cell proliferation and migration, and mechanisms of CDH2 expression.

LncRNAs are a class of non-coding RNAs that play an important role in regulating gene expression. However, their specific molecular mechanisms in gastric carcinogenesis and metastasis need further exploration. TCGA data showed that the expression of MFGE8, which was closely related to survival, was significantly positively correlated with lncRNA SNHG14. And moreover, the results of high-throughput sequencing and qRT-PCR showed that lncRNA SNHG14 was significantly elevated in gastric cancer. Further, in vitro functional realization showed that lncRNA SNHG14 overexpression significantly increased gastric cancer's proliferation, invasion and migration. Animal experiments also showed that lncRNA SNHG14 overexpression promoted tumorigenesis and metastasis in vivo. Mechanistically, MFGE8 activates the expression of lncRNA SNHG14, which activates the cellular EMT by stabilizing CDH2. Our study suggests that lncRNA SNHG14 could be a potential target for gastric cancer therapy.

Gastric cancer is one of the malignant tumors with a high incidence and high mortality rate worldwide. The current treatment modalities for gastric cancer are surgery, chemotherapy and targeted therapy. However, the 5-year survival rate of gastric cancer patients is still less than 30%. The main reason for the low survival rate of gastric cancer patients is that most cases are already at an advanced disease stage when first diagnosed, with tumor metastasis, tumor heterogeneity and resistance to radiotherapy. TCGA data showed that the expression of MFGE8, which was closely related to survival, was significantly positively correlated with lncRNA SNHG14.We found that lncRNA SNHG14 expression was significantly elevated in gastric cancer by high-throughput sequencing. It was further confirmed in vitro and in vivo that overexpression of lncRNA SNHG14 promoted the proliferation and migration ability of gastric cancer. Mechanistically, lncRNA SNHG14 played an oncogene role by promoting CDH2 expression to activate EMT in tumor cells.

Dexmedetomidine Promoted HSPB8 Expression via Inhibiting the lncRNA SNHG14/UPF1 Axis to Inhibit Apoptosis of Nerve Cells in AD : The Role of Dexmedetomidine in AD.

Dexmedetomidine (Dex) is reported to play a neuroprotective role in Alzheimer's disease (AD). However, the specific mechanism remains unclear. Figure out the underlying molecular mechanism of Dex regulating nerve cell apoptosis in the AD model. The AD model in vitro was established after SH-SY5Y cells were treated with Aß1 - 42 at (10 µM) for 24 h. The interaction among UPF1, lncRNA SNHG14, and HSPB8 was verified by RIP assay. Cell viability, apoptosis, the level of genes, and proteins were detected by CCK-8 assay, flow cytometry, Western blot, and qRT-PCR, respectively. Dex downregulated lncRNA SNHG14 level and inhibited apoptosis of nerve cells. LncRNA SNHG14 overexpression reversed the inhibitory effect of Dex on nerve cell apoptosis in the AD model. LncRNA SNHG14 attenuated HSPB8 mRNA stability by recruiting UPF1. HSPB8 overexpression inhibited apoptosis of nerve cells in the AD model. Moreover, HSPB8 knockdown reversed the inhibitory effect of Dex on nerve cell apoptosis in the AD model. Our study demonstrated that Dex promoted HSPB8 expression via inhibiting the lncRNA SNHG14/UPF1 axis to inhibit nerve cell apoptosis in AD.

LncRNA SNHG14 promotes cell proliferation and invasion in colorectal cancer through modulating miR-519b-3p/DDX5 axis.

Numbers of studies suggest that long non-coding RNAs (lncRNAs) exert an important role in cancer progression. It is reported that lncRNA SNHG14 (SNHG14) promotes cell proliferation and invasion in many cancers. However, the underlying molecular mechanism of SNHG14 in colorectal cancer (CRC) remains unclear. In our study, we found that SNHG14 is highly expressed in CRC tissues and cells, especially in SW480 and HT-29 cells. In addition, sh-SNHG14 inhibits cell proliferation, cell migration and invasion, promotes cell apoptosis in CRC cell lines. Furthermore, we found that SNHG14 functions as a sponge for miR-519b-3p, while the DEAD box protein 5 (DDX5) is a downstream target gene of miR-519b-3p, and the functions of miR-519b-3p inhibitors on the CRC progression could be rescued by downregulation of DDX5. Our findings suggest that SNHG14 promotes the CRC progression by miR-519b-3p/DDX5 axis, implying the promising therapeutic target of SNHG4 for CRC patients.

lncRNA SNHG14 promotes oncogenesis and immune evasion in diffuse large-B-cell lymphoma by sequestering miR-152-3p.

This study aimed to explore the role of small nucleolar RNA host gene 14 (SNHG14) in the pathogenesis of diffuse large-B-cell lymphoma (DLBCL). DLBCL cell lines (OCI-Ly7 and OCI-Ly3) and specimens from patients were collected to evaluate the roles of SNHG14 in DLBCL pathogenesis. The results showed that SNHG14 expression increased and miR-152-3p expression decreased in DLBCL tissues and cell lines, indicating a negative correlation between miR-152-3p and SNHG14 expression. Moreover, SNHG14 was found to promote DLBCL growth, migration, and EMT-like processes in vitro, and directly inhibits miR-152-3p gene expression via sequestration of the miR-152-3p transcripts in DLBCL. Additionally, SNHG14/miR-152-3p inhibits apoptosis and promotes cell proliferation on cytotoxic T lymphocytes (CTLs) in DLBCL via the PD-1/PD-L1 checkpoint. Furthermore, both the immune escape and progression of DLBCL are advanced by SNHG14 expression via its interactions with miR-152-3p. Collective, this suggests that SNHG14 is a potential diagnostic, prognostic, and therapeutic target for DLBCL.

Downregulation of lncRNA SNHG14 attenuates osteoarthritis by inhibiting FSTL-1 mediated NLRP3 and TLR4/NF-κB pathway through miR-124-3p.

Osteoarthritis (OA) is the joint pain and dysfunction syndrome caused by severe joint degeneration. The overproduced inflammatory mediators contribute greatly to OA development. It is reported that long non-coding RNA (lncRNA) takes part in many inflammatory diseases. Here, we mainly explored the function of lncRNA SNHG14 in OA process and its specific mechanisms. An OA rat model was induced by destabilizing the medial meniscus (DMM) and IL-1ß (5 ng/mL) was used to mediate an OA cell model in particular chondrocytes (AC). Gain- or loss-of functional assays of SNHG14 and miR-124-3p were carried out to explore their roles in OA development. The experimental statistics illustrated that lncRNA SNHG14 and IL-1ß mRNA expression were both increased in OA tissues, while miR-124-3p was lowly-expressed. Linear regression analysis showed that SNHG14 and miR-124-3p had negative relationship in the OA tissues. In the in vitro experiments, downregulation of lncRNA SNHG14 promoted the proliferation of IL-1ß-treated AC and inhibited cell apoptosis and COX-2, iNOS, TNF-α, IL-6 expression. Moreover, lncRNA SNHG14 inhibited miR-124-3p expression as a miRNA sponge. MiR-124-3p targeted the 3'non-translated region (3'UTR) of FSTL-1 and TLR4 and inhibited their expressions. Also, the in vivo experiments confirmed that knocking down SNHG14 relieved the progression of OA in rats via inhibiting inflammatory responses. In conclusion, this study confirmed that downregulation of lncRNA SNHG14 inhibits FSTL-1-mediated activation of NLRP3 and TLR4/NF-κB signalling pathway activation by targeting miR-124-3p, thus attenuating inflammatory reactions in OA.

LncRNA SNHG14 contributes to the progression of NSCLC through miR-206/G6PD pathway.

BACKGROUND: Previous studies have shown that the dysregulation of lncRNAs participates in non-small cell lung cancer (NSCLC) development. The purpose of this study was to research the biological function of lncRNA SNHG14 and its molecular mechanism in NSCLC progression. METHODS: RT-PCR was applied for investigating the expression of SNHG14, miR-206 and G6PD. The progression of NSCLC was detected by CCK-8, Transwell and western blot assays. The targets of SNHG14 and miR-206 were measured by dual-luciferase reporter assay. RESULTS: We found a higher expression of SNHG14 in NSCLC and upregulation of SNHG14 contributed to NSCLC cell proliferation, invasion and migration. However, knockdown of SNHG14 showed the opposite effect on the progression of NSCLC. Specifically, SNHG14 negatively regulated miR-206 expression by binding with it directly. Furthermore, G6PD served as the target of miR-206. Rescue experiments showed that SNHG14 promoted G6PD expression by inhibiting miR-206. CONCLUSIONS: LncRNA SNHG14 contributed to NSCLC progression through miR-206/G6PD axis, providing novel clues for understanding the mechanism of NSCLC.

Long Non-Coding RNA SNHG14 Regulates SPIN1 Expression to Accelerate Tumor Progression in Non-Small Cell Lung Cancer by Sponging miR-382-5p.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung carcinoma. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) was identified to participate in tumor progression. However, the mechanism and functions of SNHG14 were rarely reported in NSCLC progression. METHODS: The relative gene expression was tested by qRT-PCR. Cell viability, apoptosis, migration and invasion were measured by MTT assay, flow cytometry, and transwell migration and invasion assays, respectively. The interactions between miR-382-5p and SNHG14 or SPIN1 were predicted by starBase and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. The protein level of SPIN1 was evaluated by Western blot assay. RESULTS: The levels of SNHG14 and SPIN1 were significantly increased, while the level of miR-382-5p was apparently reduced in NSCLC tissues and cells. SNHG14 was verified to sponge miR-382-5p and SPIN1 was identified as a direct target of miR-382-5p. SNHG14 depletion repressed cell viability, migration and invasion, but induced the apoptotic rate by targeting miR-382-5p. miR-382-5p overexpression blocked cell viability, metastasis and promoted cell apoptosis by regulating SPIN1. SNHG14 silencing down-regulated SPIN1 expression by sponging miR-382-5p. CONCLUSION: SNHG14 facilitated NSCLC progression by regulating SPIN1 expression via targeting miR-382-5p.

SP1-induced up-regulation of lncRNA SNHG14 as a ceRNA promotes migration and invasion of clear cell renal cell carcinoma by regulating N-WASP.

Clear cell renal cell carcinoma (ccRCC) is one of the leading causes of genitourinary cancer-related death, largely due to the metastasis of ccRCC. Previous profiling study showed that lncRNAs are critical regulators in lots of cancers. However, the roles of specific lncRNAs in ccRCC migration and invasion are still unknown. In this study, we utilized the high-throughput genome sequencing to identify the potential differentially expressed lncRNAs in ccRCC and further determined the underlying regulatory mechanism. We found that lncRNA SNHG14 was significantly up-regulated in ccRCC cell lines in contrast to normal renal epithelial cells. By performing bioinformatics analysis and luciferase reporter assays, we revealed that the transcription factor SP1 can bind to the promoter region of SNHG14, resulting in the overexpression of SNHG14 in ccRCC. Functionally, enhanced expression of lncRNA SNHG14 promoted cell migration and invasion through promoting N-WASP protein level. More importantly, RT-qPCR and in situ RNA FISH analysis showed that SNHG14 was predominantly abundant in the cytoplasm of ccRCC cells. The subsequent RNA immunoprecipitation assay, and gain or loss-function assays showed that SNHG14 functioned as ceRNA to regulate N-WASP expression and cell motility ability via a miR-203-dependent manner. Our results imply that SNHG14 is a critical lncRNA that promotes ccRCC migration and invasion via sponging miR-203 and elevating N-WASP. Therefore, SNHG14 could serve as a promising therapeutic target for ccRCC.