lncRNA SNHG1 Research Articles

SNHG17 Reprograms Energy Metabolism of Breast Cancer by Activating Mitochondrial DNAs Transcription.

In most solid tumors, cellular energy metabolism is primarily dominated by aerobic glycolysis, which fulfills the high demand for biomacromolecules at the expense of reduced ATP production efficiency. Elucidation of the mechanisms by which rapidly proliferating malignant cells acquire sufficient energy in this state of inefficient ATP production from glycolysis could enable development of metabolism targeted therapeutic strategies. In this study, we observed a significant association between elevated expression levels of the long non-coding RNA (lncRNA) SNHG17 and unfavorable prognosis in breast cancer (BCa). SNHG17 promoted BCa cell proliferation by augmenting mitochondrial ATP production. Mechanistically, SNHG17 directly interacted with the p65 subunit of NF-κB and phosphorylated p65 at the threonine 505 site. SNHG17 bound to p65 at its truncated loop2 site, recruited p65 to mitochondria, and co-regulated the transcriptional activation of mitochondrial DNA to promote ATP production. Accordingly, targeting SNHG17 with an anti-sense oligonucleotide (ASO) significantly reduced BCa tumor growth both in vitro and in vivo. Overall, these results established a role for SNHG17 in promoting BCa progression by increasing ATP production and provided insight into the reprogramming of energy metabolism in solid tumors.

LncRNA SNHG6 Knockdown Promotes Microglial M2 Polarization and Alleviates Spinal Cord Injury via Regulating the miR-182-5p/NEUROD4 Axis.

Spinal cord injury (SCI) is one of the devastating neurological disorders that leads to a loss of motor and sensory functions. Long non-coding RNA small nucleolar RNA host gene 6 (lncRNA SNHG6) plays a crucial role in inflammatory regulation across various diseases. This study investigates the role of SNHG6 in SCI development and its underlying regulatory mechanisms. Two experimental models were established: an in vitro model using LPS-challenged (100ng/mL) mouse microglia BV2 cells and an in vivo model employing controlled spinal cord impact in mice. SNHG6, miR-182-5p, and NEUROD4 expression levels were quantified through RT-qPCR and Western blot. Functional and histological assessments were performed using the Basso mouse scale (BMS) and Nissl staining, respectively. Putative binding sites between SNHG6 and miR-182-5p, as well as between miR-182-5p and NEUROD4, were predicted using the ENCORI/starBase platform. These molecular interactions were validated through dual-luciferase reporter assays and RNA pull-down experiments, with further confirmation by qRT-PCR and Western blot analyses. Both LPS-stimulated BV2 cells and spinal cord tissues from SCI mice exhibited elevated SNHG6 expression. Downregulation of SNHG6 enhanced LPS-induced polarization of BV2 cells from M1-type to M2-type, significantly modulated the expression of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) and anti-inflammatory factors (TGF-β, IL-10, and IL-13), and reduced injury severity in SCI mice. Our mechanistic studies revealed that SNHG6 functions as a molecular sponge for miR-182-5p to regulate NEUROD4 expression. This study demonstrates that SNHG6 knockdown promotes microglial M2-type polarization and alleviates inflammatory responses through modulation of the miR-182-5p/NEUROD4 axis, suggesting SNHG6 as a potential therapeutic target for SCI treatment.

LncRNA SNHG5 induces CAFs-like phenotype and autophagy of AML-MSCs via PTBP1/ATG5 axis to confer chemoresistance of AML cells.

Acute myeloid leukemia (AML) is still a threaten to human health due to its high occurrence and poor prognosis. Mesenchymal stem cells (MSCs) in bone marrow microenvironment (BMM) play a critical role in the development of AML. This study elucidated the interaction between MSCs and AML cells and its underlying mechanism. MSCs were isolated, identified, and co-cultured with AML cells. qRT-PCR, Western blotting and immunofluorescence were used to determine molecule expression. Cell viability and apoptosis were determined by CCK-8 and flow cytometry. Exosomes were isolated and characterized, and PKH26 was used for monitoring exosome internalization. RNA-FISH was used to determine the localization of SNHG5. RIP, RNA-pull down and ChIP assays were used to evaluate the molecular interaction. SNHG5 expression was up-regulated and positively correlated with cancer-associated fibroblasts (CAFs)-related biomarkers in MSCs. AML cells-derived exosomes delivered SNHG5 to enhance its expression in MSCs. SNHG5 overexpression induced CAFs-like phenotype and autophagy in MSCs that led to daunorubicin resistance of AML cells. Mechanistically, SNHG5 stabilized autophagy related 5 (ATG5) mRNA by interaction with polypyrimidine tract-binding protein 1 (PTBP1). AML cells-derived exosomal lncRNA SNHG5 triggered CAFs-like phenotype and autophagy of AML-MSCs via interaction with PTBP1 to increase ATG5 mRNA stability, thereby leading to chemoresistance of AML cells.

LncRNA SNHG16 Drives PD-L1-Mediated Immune Escape in Colorectal Cancer through Regulating miR-324-3p/ELK4 Signaling.

Colorectal cancer (CRC) is a common malignancy that claims the life of many patients. Nucleolar RNA host gene 16 (SNHG16) has been identified as an oncogene in CRC development. However, the role and mechanism of SNHG16 in CRC remain unclear. A total of 27 cases of CRC tumor tissues and adjacent tissues were collected to investigate the expression and correlation among SNHG16, miR-324-3p, ELK4 and PD-L1 using qRT-PCR, western blot and Pearson analysis. Cell proliferation, migration and invasion abilities were determined using CCK-8 and transwell assays. The cytotoxicity of CD8 + T cells and the apoptosis of CD8+ T cells was evaluated by LDH assay and flow cytometry, respectively. Dual luciferase assay, RIP and ChIP methods were performed to verify molecular interactions. Our results showed that SNHG16, ELK4 and PD-L1 expression were abnormally elevated and miR-324-3p expression was decreased in tumor tissues from CRC patients and CRC cells. SNHG16 silencing resulted in suppression of cell growth, metastasis, and immune escape of CRC cells, which was reversed by miR-324-3p inhibitor and ELK4 overexpression. Mechanistically, SNHG16 acted as a competitive endogenous RNA to enhance ELK4 expression by sponging miR-324-3p, thereby provoking the transcription of PD-L1. Our results demonstrated that SNHG16 silencing led to the suppression of cell growth, metastasis, and immune escape of CRC cells through mediating miR-324-3p/ELK4/PD-L1 axis, offering promising targets for CRC treatment.

The Prognostic Value and Clinical Significance of lncRNA SNHG5 Expression in Patients with Multiple Malignancies: A Bioinformatic and Meta-analysis.

Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) has been identified as both a promising target for treatment and a predictor of prognosis in diverse types of cancer. The objective of this study was to assess whether lncRNA SNHG5 expression can be utilized as a prognostic biomarker for human cancer. To ensure a thorough search of the literature for relevant English studies published before July 2023, several databases were searched, including PubMed, Web of Science, ProQuest, Cochrane Library, and Google Scholar. The study evaluated the impact of lncRNA SNHG5 on the overall survival (OS) of cancer by calculating the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). To further confirm the accuracy of the findings, the study investigated the expression profile and prognostic significance of lncRNA SNHG5 through the use of GenomicScape, OncoLnc, Kaplan-Meier plotter, and GEPIA databases. In this study, 995 patients were examined across a total of fourteen original studies. The findings indicated that there was a significant relationship between heightened lncRNA SNHG5 expression and reduced OS, as evidenced by both univariate and multivariate analyses (HR = 1.89; 95% CI, 1.44-2.49; p < 0.001; HR = 3.97; 95% CI, 1.80-8.73; p < 0.001, respectively). Pooled OR analysis showed a significant association between over-expression of lncRNA SNHG5 with advanced histological grade (OR = 0.28; 95% CI, 0.11-0.71; p = 0.007), present lymph node metastasis (LNM; OR = 4.28; 95% CI, 2.47-7.43; p < 0.001), and smoking history (OR = 0.27; 95% CI, 0.15-0.49; p < 0.001). Bioinformatic databases confirmed that elevated SNHG5 expression was significantly linked to poor prognosis in cancer patients, including colorectal cancer (CRC), acute myeloid leukemia (AML), and esophageal adenocarcinoma (ESAD), and a longer OS in patients with uterine corpus endometrial carcinoma (UCEC). These results suggest that lncRNA SNHG5 may serve as an adverse prognostic biomarker in several human cancers. Further investigations are needed to better understand the underlying mechanisms that link lncRNA SNHG5 to multiple malignancies.

Long Non-Coding RNA SNHG3 Promotes the Progression of Cholangiocarcinoma by Regulating the miR-151a-3p/STAT5a Axis.

Studies have shown the significance of long non-coding RNAs (lncRNAs) in the development of malignant tumors, including cholangiocarcinoma (CCA). However, the molecular mechanisms through which the lncRNA SNHG3 contributes to CCA development remain unknown. Therefore, the purpose of this work was to investigate SNHG3's role and possible processes in CCA. CCK-8, TUNEL, wound healing, and transwell assays were performed to evaluate the viability, apoptosis, migration, and invasion of CCA cells, respectively. Dual-luciferase reporter and RNA pull-down assays were conducted to verify the relationship between SNHG3 and miR-151a-3p and that between STAT5a and miR-151a-3p. SNHG3 and STAT5a were considerably upregulated and miR-151a-3p was downregulated in CCA tissues and cells. SNHG3 knockdown suppressed the proliferation, apoptosis, migration, and invasive ability of HUCC-T1 cells. Mechanistically, SNHG3 directly targeted miR-151a-3p to promote the development of CCA. Treatment with a miR-151a-3p inhibitor reversed the effects of SNHG3 knockdown on the aggressive behavior of HUCC-T1 cells. Furthermore, STAT5a knockdown counteracted the effects of inhibition of SNHG3 and miR-151a-3p on the aggressive behavior of CAA. SNHG3 promotes CCA progression via the miR-151a-3p/STAT5a axis, providing novel insights into the clinical treatment of CCA.

SNHG12 in cancer-associated fibroblast-derived extracellular vesicle induces macrophage-myofibroblast transition.

To investigate mechanism of lncRNA SNHG12 induced macrophage-myofibroblast transition (MMT) in cancer-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) in non-small cell lung cancer (NSCLC). CAFs EVs were isolated from human NSCLC tissue and adjacent cancerous tissue (n = 3), and their morphology and particle size were evaluated. Macrophages and MMT cells with different phenotypes were detected, and the binding relationship of lncRNA SNHG12, miR-181a-5p, and Smad3 was verified. LncRNA SNHG12 derived from CAFs-EVs promoted the transformation of M2 macrophages into MMT. In addition, lncRNA-SNHG12 increased the expression of Smad3 which was significantly upregulated in MMT through sponge of miR-181a-5p. LncRNA SNHG12 derived from CAFs-EV induced MMT in NSCLC.

Methylation of long non-coding rna genes: &lt;i&gt;SNHG6, SNHG12, TINCR&lt;/i&gt; in ovarian cancer

Ovarian cancer (OC) develops asymptomatically and is not diagnosed until advanced stages, which increases the mortality rate from this disease. In the diagnosis and treatment of OC, new prospects have been opened in studies of the gene regulation mechanisms involving long non-coding RNAs (lncRNAs) and identification of lncRNA genes inhibited by methylation of promoter regions. Using a set of 122 samples of primary OC tumors, by methylation specific real-time PCR, changes in the methylation level of a group of lncRNA genes were studied: PLUT, SNHG1, SNHG6, SNHG12, and TINCR. Using the nonparametric Mann–Whitney test, a statistically significant (p 0.001) increase in the methylation level of these 5 lncRNA genes in tumors was shown. A statistically significant (p 0.05) correlation was established between the level of methylation of the lncRNA genes SNHG6, SNHG12 and TINCR with the stage of the tumor process, the histological grade and the presence of metastases. Using real-time RT-qPCR, a decrease in the expression level of the SNHG6, SNHG12 and TINCR genes was observed and a significant correlation of methylation with the expression of SNHG6 and TINCR was shown (rs ≤ −0.5, p 0.001). Thus, new lncRNA genes representing potential epigenetic markers of ovarian cancer have been identified.

Exploring lncRNA expression in follicular fluid exosomes of patients with obesity and polycystic ovary syndrome based on high-throughput sequencing technology

BackgroundInfertility is a reproductive health problem that attracts worldwide attention. Polycystic ovary syndrome (PCOS) is a major cause of female infertility and patients with obesity and PCOS are particularly common in clinical practice. Long non-coding RNA (lncRNAs) are a functional core in cells that regulate gene expression, transcription, and chromatin modification processes, and participate in epigenetics, cell cycle, and cell differentiation. LncRNAs are assumed to play a role in the occurrence and development of PCOS; however, their specific mechanism of action remains to be elucidated.MethodsHigh-throughput sequencing technology has been used to sequence and analyze lncRNAs in exosomes from the follicular fluid of patients with obesity and PCOS and those who underwent assisted reproductive therapy owing to male factors. Specific expression profiles of patients with obesity and PCOS were obtained and functional information analysis combined with a literature review were performed to screen for differentially expressed lncRNAs, which were validated using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).ResultsHigh-throughput sequencing analysis revealed that compared to normal patients with male infertility, patients with obesity and PCOS had a total of 20 lncRNAs with significant expression differences in follicular fluid exosomes. Among them, 17 lncRNAs were upregulated and three were downregulated. Functional analysis showed that differentially expressed genes were mainly enriched in “cell metabolism,” “cell adhesion,” and other aspects: related gene pathways mainly involved Huntington’s disease, Parkinson’s disease, spliceosomes, non-alcoholic fatty liver disease, and ribosomes. Verification of differentially expressed lncRNAs revealed that the expression of lncRNAs TPT1-AS1, PTOV1-AS1, PTPRG-AS1, and SNHG14 in follicular fluid exosomes was consistent with the sequencing results.ConclusionA preliminary differential expression profile of lncRNAs in exosomes of patients with obesity and PCOS was established by transcriptomic analysis of these individuals. Our bioinformatics analysis results may be applicable to further study of the impact mechanism involving obesity and PCOS. These differentially expressed lncRNAs maybe served as potential biomarkers for in-depth studies of the occurrence, development on Follicle quality and function for patients with PCOS in the future.

Potential Diagnostic Markers of Diabetic Retinopathy: Serum LncRNA MIAT, HOTTIP, SNHG16.

To study the expression and diagnostic ability of the long noncoding RNAs (lncRNAs) MIAT, HOTTIP, and SNHG16 in serum of patients with diabetic retinopathy. A total of 70healthy controls and 195 patients with Type 2 Diabetes (T2D) were collected. T2D patients include 65 patients with Nondiabetic retinopathy (NDR), 65 patients with Nonproliferative diabetic retinopathy (NPDR) and 65 patients with Proliferative diabetic retinopathy (PDR). The relative expression of MIAT, HOTTIP and SNHG16 in participant serum was measured through Real-time fluorescence quantitative polymerase chain reaction to compare the differential expression between the groups. t test, Mann‒Whitney U-test, Pearson's chi-square test and the receiver operating characteristic (ROC) curve were used to analyze the expression of these LncRNAs and their diagnostic ability for DR. We compare the healthy control group with T2D group, healthy control group with NDR group, NDR group with DR (NPDR+PDR) group, and NPDR group with PDR group. When NDR group was compared with the healthy control group, there was no difference between MIAT (p>0.05)and HOTTIP (p>0.05), only the relative expression of SNHG16(p<0.05) was different and it's ROC curve had identification significance. In the remaining inter-group comparisons, the differences in the expression of MIAT (p<0.05), HOTTIP (p<0.05) and SNHG16 (p<0.05) were statistically significant, and their ROC curves were all had identification significance. These findings prove that serum LncRNA MIAT, HOTTIP and SNHG16 may be used as potential markers to monitor the progress of DR.

Clinical significance of circulating long non-coding RNA SNHG1 in type 2 diabetes mellitus and its association with cell proliferation of pancreatic β-cell

BackgroundTo explore the association of long non-coding RNA (lncRNA) SNHG1/ miR-195 axis with type 2 diabetes mellitus (T2DM) and islet function.MethodsThe expression of SNHG1 and miR-195 was measured in T2DM patients and in healthy subjects. Correlation between indciators was evaluated using Pearson correlation analysis. INS-1 cells were used to perform the cell function assays. Insulin secretion by INS-1 was detected using ELISA. Cell counting kit-8 (CCK-8) and flow cytometry was used to detect cell proliferation and apoptosis. Luciferase report assay was to used to verify the target of SNHG1.ResultsThe expression of SNHG1 was increased and miR-195 level was decreased in the serum of T2DM patients. Both SNHG1 and miR-195 could be biomarkers for T2DM diagnosis. The fasting plasma glucose (FPG) and HbA1c were positively related to SNHG1 and negatively related to miR-195. SNHG1 inhibited insulin secretion, and cell proliferation and promoted apoptosis of INS-1 cells via binding to miR-195.ConclusionsDetection of SNHG1 and miR-195 might predict T2DM. SNHG1 could suppress proliferation and insulin secretion, but promote apoptosis of INS-1 cells via sponging miR-195.

LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling.

LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3-aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3/SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD.

LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling

LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3-aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3/SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD.

Investigating SNHG3 as a potential therapeutic approach for HCC stem cells

IntroductionHepatocellular Carcinoma (HCC) is a common malignant tumor worldwide. Long Non-Coding RNA (lncRNA) has gained attention in tumor biology, and this study aims to investigate the role of lncRNA SNHG3 in HCC, specifically in the self-renewal and maintenance of liver cancer stem cells. MethodsThe expression of lncRNA SNHG3 was analyzed in HCC and adjacent normal tissue using the TCGA database. The expression levels of SNHG3 in HCC cell lines (Hep3B, HepG2, Huh7) were detected using qRT-PCR and Western blot techniques. Functional assays, including CCK-8, soft agar colony formation, and tumor sphere formation, were performed to evaluate the impact of SNHG3 on HCC stem cell functionality. MeRIP-qPCR was also used to investigate the regulatory role of SNHG3 in m6A modification of ITGA6 mRNA mediated by METTL3. ResultsThe study found that SNHG3 was significantly upregulated in HCC tissue and cell lines compared to normal liver tissue. SNHG3 expression correlated with the pathological stage, metastasis status, and tumor size of liver cancer. Inhibiting SNHG3 reduced proliferation, colony formation, and tumor sphere formation ability in HCC stem cells. SNHG3 also played a role in regulating the m6A modification and expression of ITGA6 through METTL3. ConclusionThis study emphasizes the upregulation of lncRNA SNHG3 and its role in HCC stem cell self-renewal. SNHG3 may regulate the m6A modification of ITGA6 mRNA through its interaction with METTL3, impacting the function of liver cancer stem cells. These findings support the potential of targeting SNHG3 as a therapeutic approach for HCC.

Correlation of SNHG7 and BGL3 expression in patients with de novo acute myeloid leukemia; novel insights into lncRNA effect in PI3K signaling context in AML pathogenesis

BackgroundAcute myeloid leukemia (AML) has been identified as a top priority for discovering a reliable biomarker for treatment improvement and patient outcome prediction due to the heterogeneous nature of AML and the obstacle to find an appropriate treatment strategy for this malignancy. Considering the involvement of long noncoding RNA (lncRNA) SNHG7 and BGL3 found in various cancers, the exact expression pattern of these lncRNAs and their clinical implications in acute myeloid leukemia (AML) continue to be elusive. In order to demonstrate a possible mechanism underlying AML pathogenesis, our goal was to examine BGL3 and SNHG7 lncRNA expressions in PI3K pathway. MethodsThis case-control cross-sectional study were conducted on RNA extracted from blood samples of 30 patients diagnosed with AML (Ayatollah-Khansari hospital, Arak, Iran) and 30 (age and gender matched) healthy controls. The expression levels of SNHG7 and BGL3 lncRNAs and their target genes Akt and PTEN, were measured using qRT-PCR. Subsequently, by means of statistical analysis, we determined the plausible correlation between the expressions of the aforementioned genes and lncRNA respectively. ResultsIn AML samples, a considerable increase in the expression levels of SNHG7 lncRNA and Akr gene was accompanied by a marked reduction in the expression levels of BGL3 lncRNA and PTEN gene. Nevertheless, No significant relationship between the expression level of the indicated genes/lncRNAs and age and sex was found. The remarkable correlation between the expression of genes/lncRNAs and the blast percentage in patients was the notable point in the result of this study. ConclusionsAs the most straightforward interpretation of our results, we propose that perhaps the association between SNHG7 and BGL3 built through the interaction between Akt and PTEN may play a crucial role in the AML pathogenesis and any element of this axis could be a potential novel target for further profound treatment strategies. Nonetheless, in the context of Hematological Malignancies, particularly AML, more detailed studies are needed in this area to elucidate the precise role played by this interesting testis-specific pathway.

LncRNA-SNHG16 Protects Against Oxidative Stress-Induced Vascular Endothelial Cell Injury in Cardiovascular Diseases by Regulating the miR-23a-3p-GLS-Glutamine Metabolism Axis.

Cardiovascular diseases are disorders of the heart and vascular system that cause high mortality rates worldwide. Vascular endothelial cell (VEC) injury caused by oxidative stress (OS) is an important event in the development of various cardiovascular diseases, including ischemic heart disease. This study aimed to investigate the critical roles and molecular mechanisms of long non-coding RNA (lncRNA) SNHG16 in regulating vascular endothelial cell injury under oxidative stress. We demonstrated that SNHG16 was significantly downregulated and miRNA-23a-3p was notably induced in human vascular endothelial cells under OS. Overexpressing SNHG16 or silencing miR-23a-3p effectively mitigated the OS-induced VEC injury. Additionally, glutamine metabolism of VECs was suppressed under OS. SNHG16 protected the OS-suppressed glutamine metabolism, while miR-23a-3p functioned oppositely in VECs. Furthermore, SNHG16 downregulated miR-23a-3p by sponging miR-23a-3p, which direct targeted the glutamine metabolism enzyme, GLS. Finally, restoring miR-23a-3p in SNHG16-overexpressing VECs successfully reversed the protective effect of SNHG16 on vascular endothelial cell injury under OS. In summary, our results revealed the roles and molecular mechanisms of the SNHG16-mediated protection against VEC injury under OS by modulating the miR-23a-3p-GLS pathway.

Clinical significance and underlying mechanism of long non-coding RNA SNHG12 in lower extremity deep venous thrombosis.

D-dimer is widely used in the diagnosis of deep vein thrombosis (DVT), but the specificity is low. The study examined the diagnostic value of long non-coding RNA (lncRNA) SNHG12 in DVT, and preliminarily discussed its mechanism. SNHG12 levels were detected in 200 elderly fracture patients via RT-qPCR, including 38 DVTs. Logistic regression analysis and receiver operating characteristic (ROC) curve were applied for diagnostic value evaluation. HUVECs were used for function study. Cell proliferation, migration, apoptosis, release of inflammatory cytokines, and adhesion factors were detected. Student's t test and one-way ANOVA were applied for data comparison between two or among three or more groups. Correlation analysis of indicators was completed via Pearson's correlation analysis. Bioinformatics analysis predicted the target miRNAs and genes of SNHG12, with GO and KEGG for the function enrichment. It was found that SNHG12 was at low expression in DVT patients, and negatively correlated with D-dimer concentration (r = -0.535). SNHG12 and D-dimer were independent influence factors related to the development of DVT. SNHG12 and D-dimer combination had the best performance in DVT diagnosis. In HUVECs, SNHG12 promoted cell proliferation and migration and restricted the release of inflammatory cytokines and adhesion factors, but these influences were counteracted by miR-424-5p. A total of 208 overlapping target genes of miR-424-5p were identified, and their function was enriched in cellular cycle and senescence. PI3K-Akt signaling pathway was the most significant pathway based on KEGG results. In conclusion, SNHG12 had good diagnostic potential for DVT combined with D-dimer. SNHG12 maintains vascular endothelial cell function by acting as a competitive endogenous RNA (ceRNA) for miR-424-5p.

Construction of an endoplasmic reticulum stress and cuproptosis -related lncRNAs signature in chemosensitivity in hepatocellular carcinoma by comprehensive bioinformatics analysis

Endoplasmic reticulum stress (ERS) and cuproptosis have remarkable effects on hepatocellular carcinoma (HCC) leading to a poor prognosis. The current study aimed to explore credible signature for predicting the prognosis of HCC based on ERS and cuproptosis-related lncRNAs. In our study, clinical and transcriptomic profiles of HCC patients were obtained from the Cancer Genome Atlas (TCGA) database. An ERS and cuproptosis-related lncRNA prognostic signature, including NRAV, SNHG3, LINC00839 and AC004687.1, was determined by correlation tests, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) methods. Survival and predictive value were evaluated using Kaplan–Meier and receiver operating characteristic (ROC) curves, while calibration and nomograms curves were developed. Besides the enrichment analyses for ERS and cuproptosis-related lncRNAs, mutational status and immune status were assessed with TMB and ESTIMATE. Additionally, consensus cluster analysis was employed to compare cancer subtype differences, while drug sensitivity and immunologic efficacy were evaluated for further exploration. qRT-PCR and CCK-8 were utilized to verify the alteration of the prognostic lncRNAs expression and proliferation in vitro. High-risk groups exhibited poorer prognosis. The signature exhibited robust predictive value as an independent prognostic indicator and showed significant correlation with clinicopathological features. In the enriched analysis, biological membrane pathways were enriched. Low-risk patients had lower TMB and higher immune status. A cluster analysis revealed that cluster 2 had the best clinical immunological efficacy and most active immune function. In brief, our constructed signature with ERS and cuproptosis-related lncRNAs was associated survival outcomes of HCC, and can be used to predict the clinical classification and curative effect.

LncRNA SNHG1 knockdown attenuates lipopolysaccharide-induced acute lung injury via regulating miR199a-3p/ROCK2 axis.

Acute lung injury (ALI) is a significant health condition with notable rates of morbidity and mortality globally. Long non-coding ribose nucleic acids (lncRNAs) play vital roles in mitigating various inflammation-related diseases, including ALI. The study aimed to investigate the functional role and molecular mechanisms of lncRNA SNHG1 on ALI in lipopolysaccharide (LPS)-treated A549 cells and in LPS-induced ALI mice. The expression of SNHG1 was initially examined in LPS-treated A549 cells. We further demonstrated the critical function of SNHG1 through various cellular assessments following SNHG1 knockdown, including cell counting kit (CCK)-8 assay, flow cytometry analysis, as well as enzyme-linked immunosorbent assay (ELISA). Reducing SNHG1 levels hindered the negative effects of LPS on cell viability, apoptosis, and inflammation. Moreover, SNHG1 acted as a negative regulator for miR-199a-3p, which targeted downstream ROCK2. Depletion of miR-199a-3p or enhanced expression of ROCK2 abolished the protective effects of SNHG1 knockdown on LPS-induced apoptosis and inflammation. Consistently, silencing SNHG1 alleviated LPS-induced lung injury in mice, demonstrating its potential therapeutic benefits in managing ALI. Overall, this study sheds light on the role of SNHG1 in modulating inflammation and apoptosis in ALI through the miR-199a-3p/ROCK2 pathway, offering new insights for the treatment of this condition.

Snhg14/miR-181a-5p axis-mediated “M1” macrophages aggravate LPS-induced myocardial cell injury

An increasing number of studies have suggested that macrophages participate in sepsis-induced myocardial injury. Our study highlights the function and mechanism of the lncRNA Snhg14 in “M1” polarized macrophage-mediated myocardial cell damage. Lipopolysaccharide (LPS) was used to treat H9c2 cells to construct an in vitro myocardial injury model. M1 and M2 polarization of RAW264.7 cells were induced and the exosomes were obtained from the supernatant through ultracentrifugation. Moreover, cecal ligation and puncture (CLP) surgery was implemented to establish a mouse sepsis-induced myocardial injury model, and Snhg14 was knocked down with sh-Snhg14. The results showed that the conditioned medium (CM) and the exosomes (Exo) of M1 macrophages substantially augmented LPS-induced apoptosis and oxidative stress in myocardial cells. Notably, M1-CM and M1-Exo contributed to nearly 50 % of myocardial cell viability decline. Snhg14 was highly expressed in M1 macrophages and exosomes derived from M1-MΦ (M1-Exo). Snhg14 overexpression aggravated myocardial cell damage and increased 10 to 50 times expression of proinflammatory cytokines in MΦ. Snhg14 knockdown reversed M1-Exo-mediated myocardial cell damage and inhibited the production of proinflammatory cytokines (50 %–75 % decline) of MΦ. Moreover, Snhg14 targeted and inhibited miR-181a-5p expression. miR-181a-5p upregulation partly reversed Snhg4 overexpression-mediated myocardial cell damage and MΦ activation. In vivo, sh-Snhg14 dramatically ameliorated cardiac damage in septic mice by enhancing miR-181a-5p and inhibiting the HMGB1/NF-κB pathway. In conclusion, “M1” macrophage-derived exosomal Snhg14 aggravates myocardial cell damage by modulating the miR-181a-5p/HMGB1/NF-κB pathway.