Small Nucleolar RNA Host Gene Research Articles

Long non-coding RNA SNHG11 regulates the Wnt/β-catenin signaling pathway through rho/ROCK in trabecular meshwork cells.

Trabecular meshwork (TM) cell dysfunction is the leading cause of elevated intraocular pressure (IOP) and glaucoma. The long non-coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) is associated with cell proliferation and apoptosis, but its biological functions and role in glaucoma pathogenesis remain unclear. In the present study, we investigated the role of SNHG11 in TM cells using immortalized human TM and glaucomatous human TM (GTM3 ) cells and an acute ocular hypertension mouse model. SNHG11 expression was depleted using siRNA targeting SNHG11. Transwell assays, quantitative real-time PCR analysis (qRT-PCR), western blotting, and CCK-8 assay were used to evaluate cell migration, apoptosis, autophagy, and proliferation. Wnt/β-catenin pathway activity was inferred from qRT-PCR, western blotting, immunofluorescence, and luciferase reporter and TOPFlash reporter assays. The expression of Rho kinases (ROCKs) was detected using qRT-PCR and western blotting. SNHG11 was downregulated in GTM3 cells and mice with acute ocular hypertension. In TM cells, SNHG11 knockdown inhibited cell proliferation and migration, activated autophagy, and apoptosis, repressing the Wnt/β-catenin signaling pathway, and activated Rho/ROCK. Wnt/β-catenin signaling pathway activity increased in TM cells treated with ROCK inhibitor. SNHG11 regulated Wnt/β-catenin signaling through Rho/ROCK by increasing GSK-3β expression and β-catenin phosphorylation at Ser33/37/Thr41 while decreasing β-catenin phosphorylation at Ser675. We demonstrate that the lncRNA SNHG11 regulates Wnt/β-catenin signaling through Rho/ROCK via β-catenin phosphorylation at Ser675 or GSK-3β-mediated phosphorylation at Ser33/37/Thr41, affecting cell proliferation, migration, apoptosis, and autophagy. Through its effects on Wnt/β-catenin signaling, SNHG11 is implicated in glaucoma pathogenesis and is a potential therapeutic target.

SNHG18 inhibits bladder cancer cell proliferation by increasing p21 transcription through destabilizing c-Myc protein

BackgroundLong non-coding RNAs (lncRNAs) have been confirmed to play important roles in various cancers including bladder cancer (BC). The precise expression pattern of lncRNA small nucleolar RNA host gene 18 (SNHG18) in BC and its mechanisms of action have not been fully explored.Materials and methodsThe expression of SNHG18 was evaluated by RT-qPCR in bladder cancer clinical samples and human bladder cancer cell lines, and stable cell lines overexpressing SNHG18 were constructed. The effect of SNHG18 on the proliferation of bladder cancer cells was detected by soft agar colony formation test, ATP activity test and subcutaneous tumorigenesis model in nude mice. The specific mechanism of SNHG18 inhibition of bladder cancer proliferation was studied by flow cytometry, western blotting, dual luciferase reporter gene assay and protein degradation assay.ResultsWe found that SNHG18 is significantly downregulated in BC tissues and cell lines. Kaplan–Meier analysis showed that SNHG18 expression is positively correlated with survival in BC patients. Ectopic overexpression of SNHG18 significantly inhibited the proliferation of BC cells in vitro and in vivo. Further mechanistic investigations demonstrated that SNHG18 inhibited c-Myc expression by modulating the ubiquitination-proteasome pathway and that c-Myc is the critical transcription factor that mediates SNHG18 inhibition of BC growth by directly binding to the p21 promoter, which was attributed with significant p21 accumulation.ConclusionsSNHG18 promotes the transcription and expression of p21 by inhibiting c-Myc expression, leading to G0-G1 arrest and inhibiting the proliferation of bladder cancer cells. These findings highlight a novel cell cycle regulatory mechanism involving the SNHG18/c-Myc/p21 pathway in BC pathogenesis and could potentially lead to new lncRNA-based diagnostics and/or therapeutics for BC.

SnoRNA and lncSNHG: Advances of nucleolar small RNA host gene transcripts in anti-tumor immunity.

The small nucleolar RNA host genes (SNHGs) are a group of genes that can be transcript into long non-coding RNA SNHG (lncSNHG) and further processed into small nucleolar RNAs (snoRNAs). Although lncSNHGs and snoRNAs are well established to play pivotal roles in tumorigenesis, how lncSNHGs and snoRNAs regulate the immune cell behavior and function to mediate anti-tumor immunity remains further illustrated. Certain immune cell types carry out distinct roles to participate in each step of tumorigenesis. It is particularly important to understand how lncSNHGs and snoRNAs regulate the immune cell function to manipulate anti-tumor immunity. Here, we discuss the expression, mechanism of action, and potential clinical relevance of lncSNHGs and snoRNAs in regulating different types of immune cells that are closely related to anti-tumor immunity. By uncovering the changes and roles of lncSNHGs and snoRNAs in different immune cells, we aim to provide a better understanding of how the transcripts of SNHGs participate in tumorigenesis from an immune perspective.

Long Non-Coding RNA Small Nucleolar RNA Host Gene 4 Induced by Transcription Factor SP1 Promoted the Progression of Nasopharyngeal Carcinoma Through Modulating microRNA-510-5p/Centromere Protein F Axis.

Long non-coding RNAs (LncRNAs) are implicated with tumorigenesis and the development of nasopharyngeal carcinoma (NPC). Previous studies suggested that long non-coding RNA small nucleolar RNA host gene 4 (SNHG4) exerted oncogenic roles in various cancers. However, the function and molecular mechanism of SNHG4 in NPC have not been investigated. In our study, it was confirmed that the SNHG4 level was enriched in NPC tissues and cells. Functional assays indicated that SNHG4 depletion inhibited the proliferation and metastasis but promoted apoptosis of NPC cells. Furthermore, we identified miR-510-5p as a downstream gene of SNHG4 in NPC cells and SNHG4 upregulated CENPF expression by binding to miR-510-5p. Moreover, there was a positive (or negative) association between CENPF and SNHG4 (or miR-510-5p) expression in NPC. In addition, rescue experiments verified that CENPF overexpression or miR-510-5p silencing abrogated inhibitory effects on NPC tumorigenesis caused by SNHG4 deficiency. The study demonstrated that SNHG4 promoted NPC progression via miR-510-5p/CENPF axis, providing a novel potential therapeutic target for NPC treatments.

Association between small nucleolar RNA host gene expression and survival outcome of colorectal cancer patients: A meta-analysis based on PRISMA and bioinformatics analysis.

Growing evidence shows that long non-coding RNA small nucleolar RNA host genes (lncRNA SNHGs) enact an pivotal regulatory roles in the shorter survival outcome of colorectal cancer (CRC). However, no research has systematically evaluated the correlation among lncRNA SNHGs expression and survival outcome of CRC. This research indented to screen whether exist potential prognostic effect of lncRNA SNHGs in CRC patientss using comprehensive review and meta-analysis. Systematic searches were performed from the six relevant databases from inception to October 20, 2022. The quality of published papers was evaluated in details. We pooled the hazard ratios (HR) with 95% confidence interval (CI) through direct or indirect collection of effect sizes, and odds ratios (OR) with 95% CI by collecting effect sizes within articles. Detailed downstream signaling pathways of lncRNA SNHGs were summarized in detail. 25 eligible publications including 2,342 patients were finally included to appraise the association of lncRNA SNHGs with prognosis of CRC. Elevated lncRNA SNHGs expression was revealed in colorectal tumor tissues. High lncSNHG expression means bad survival prognosis in CRC patients (HR=1.635, 95% CI: 1.405-1.864, P<0.001). Additionally, high lncRNA SNHGs expression was inclined to later TNM stage (OR=1.635, 95% CI: 1.405-1.864, P<0.001), distant lymph node invasion, distant organ metastasis, larger tumor diameter and poor pathological grade. Begg's funnel plot test using the Stata 12.0 software suggested that no significant heterogeneity was found. Elevated lncRNA SNHGs expression was revealed to be positively correlated to discontented CRC clinical outcome and lncRNA SNHG may act as a potential clinical prognostic index for CRC patients.

Tobacco nicotine promotes TRAIL resistance in lung cancer through SNHG5.

Tobacco nicotine use is carcinogenic and a well-known risk factor for lung cancer. However, whether tobacco nicotine can induce drug resistance in lung cancer is not clear. The objective of the present study was to identify the TNF-related apoptosis-inducing ligand (TRAIL) resistance of long noncoding RNAs (lncRNAs) that are differentially expressed in smokers and nonsmokers with lung cancer. The results suggested that the nicotine upregulated small nucleolar RNA host gene 5 (SNHG5) and markedly decreased the levels of cleaved caspase-3. The present study found that cytoplasm lncRNA SNHG5 overexpression was associated with TRAIL resistance in lung cancer and that SNHG5 can interact with X-linked inhibitor of apoptosis protein to promote TRAIL resistance. Therefore, nicotine promoted TRAIL resistance in lung cancer through SNHG5/X-linked inhibitor of apoptosis protein.

SNHG1 functions as a ceRNA in hypertrophic scar fibroblast proliferation and apoptosis through miR-320b/CTNNB1 axis.

Hypertrophic scar (HS) is a fibrotic disease caused by skin injury. Competing endogenous RNA (ceRNA) has been demonstrated to implicate in the regulation of cell malignant phenotypes. This research aims to reveal the effect of catenin beta 1 (CTNNB1) on the functions of hypertrophic scar fibroblasts (HSFBs) and its role in a ceRNA network. RNA expression level was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proliferation and apoptosis of HSFB was detected via Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. Mechanism experiments included RNA pull down assay, luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were applied to analyze the upstream molecular mechanism of CTNNB1. CTNNB1 was highly expressed in HSFB. CTNNB1 depletion repressed malignant growth of HSFB. Mechanically, CTNNB1 was targeted by microRNA-320b (miR-320b) in HSFB. Small nucleolar RNA host gene 1 (SNHG1) aced as a ceRNA to upregulate CTNNB1 expression via sponging miR-320b in HSFB. CTNNB1 overexpression could reverse the impact of SNHG1 depletion on the proliferation and apoptosis of HSFB. SNHG1 acts as a ceRNA in modulating HSFB proliferation and apoptosis through miR-320b/CTNNB1 axis. SNHG1 act as a ceRNA to promote HSFB growth by sponging miR-320b to upregulate CTNNB1.

The Diagnostic and Therapeutic Role of snoRNA and lincRNA in Bladder Cancer

Bladder cancer is one of the most common malignancies of the urinary tract and can be divided into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Although the means of diagnosis and treatment have continually improved in recent years, the recurrence rate of bladder cancer remains high, and patients with MIBC typically have an unfavourable prognosis and a low quality of life. Emerging evidence demonstrates that long noncoding RNAs play a crucial role in the carcinogenesis and progression of bladder cancer. Long intergenic noncoding RNAs (lincRNAs) are a subgroup of long noncoding RNAs (lncRNAs) that do not overlap protein-coding genes. The potential role of lincRNAs in the regulation of gene expression has been explored in depth in recent years. Small nucleolar RNAs (snoRNAs) are a class of noncoding RNAs (ncRNAs) that mainly exist in the nucleolus, are approximately 60-300 nucleotides in length, and are hosted inside the introns of genes. Small nucleolar RNA host genes (SNHGs) have been associated with the origin and development of bladder cancer. In this review, we aim to comprehensively summarize the biological functions of these molecules in bladder cancer.

LncRNA SNHG1 promotes nasopharyngeal carcinoma development via targeting miR-424-5p.

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck. Distant metastasis and drug resistance are the main causes of cancer-related death. A better understanding of the molecular mechanisms that affect the progression of NPC would contribute to clinical treatment. This paper aims to investigate the effects of the long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) on biological phenotypes of NPC cells and its related mechanisms. The expression of SNHG1 and miR-424-5p in non-cancerous nasopharyngeal mucosa tissues and NPC tissues, as well as in normal nasopharyngeal epithelial cells and NPC cells was detected by qRT-PCR. HK1 and C666-1 cells were transfected with SNHG1 overexpression vector (OE-SNHG1), miR-424-5p mimic, SNHG1 knockdown vector (sh-SNHG1), or miR-424-5p inhibitor, followed by detection of transfection efficiency by qRT-PCR, cell viability by MTT, and invasive and migratory abilities by transwell invasion assay and cell scratch test. Moreover, the relationship between SNHG1 and miR-424-5p was detected by dual-luciferase reporter and RIP assays. In NPC tissues and cells, SNHG1 was upregulated but miR-424-5p was downregulated. Transfection with OE-SNHG1 or miR-424-5p inhibitor promoted proliferative, invasive, and migratory phenotypes of HK1 and C666-1 cells; transfection of sh-SNHG1 or mi-miR-424-5p induced reverse trends. Mechanistically, SNHG1 negatively regulated miR-424-5p expression, and transfection of miR-424-5p inhibitor counteracted the inhibitory effects of sh-SNHG1 on the proliferative, invasive, and migratory phenotypes of HK1 and C666-1 cells. LncRNA SNHG1 promoted proliferation, invasion and migration of NPC cells by repressing miR-424-5p expression.

Promoting action of long non-coding RNA small nucleolar RNA host gene 4 in ovarian cancer.

Long non-coding RNA (LncRNA) small nucleolar RNA host gene 4 (SNHG4) has been shown to be aberrantly expressed in a variety of cancers and involved in cancer development, but its role in ovarian cancer (OC) is unclear. The purpose of this study was to explore the biological function of SNHG4 in OC and reveal its potential downstream molecular targets. OC tumor tissue and normal tissue were collected; normal human ovarian epithelial cell line (IOSE80) and human ovarian cancer cell line (A2780, SKOV-3, OV-90 and CAOV3) were selected. RT-qPCR was used to detect SNHG4, miR-98-5p, and TMED5, while western blot was used to detect the protein expression levels of TMED5, Ki67, MMP-9, Bcl-2, Bax, Gsk3β, Wnt3a, and β-catenin. The subcellular localization of SNHG4 was assessed by nucleocytoplasmic separation assay. CCK-8, colony formation assay, flow cytometry, and Transwell were used to assess the biological behavior of OC cells. The targeting relationship between SNHG4, miR-98-5p and TMED5 was verified by dual luciferase reporter assay and RIP assay. In OC, SNHG4 and TMED5 were highly expressed, and miR-98-5p was underexpressed. Knockdown of SNHG4 inhibited OC cell proliferation, migration and invasion, promoted apoptosis, and prevented Wnt/β-catenin pathway activation. The effect of knockdown of SNHG4 was reversed by knockdown of miR-98-5p or overexpression of TMED5. Mechanistically, SNHG4 competitively adsorbed miR-98-5p to mediate TMED5 expression, thereby activating the Wnt/β-catenin pathway. SNHG4 accelerates OC development via mediating the miR-98-5p/TMED5 axis and activating the Wnt/β-Catenin pathway. SNHG4 gene silencing might be a novel option for OC treatment.

LncRNA SNHG5 Suppresses Cell Migration and Invasion of Human Lung Adenocarcinoma via Regulation of Epithelial-Mesenchymal Transition.

Long noncoding RNAs (lncRNAs) are gradually being annotated as important regulators of multiple cellular processes. The goal of our study was to investigate the effects of the lncRNA small nucleolar RNA host gene 5 (SNHG5) in lung adenocarcinoma (LAD) and its underlying mechanisms. The findings revealed a substantial drop in SNHG5 expression in LAD tissues, which correlated with clinical-pathological parameters. Transcriptome sequencing analysis demonstrated that the inhibitory effect of SNHG5 was associated with cell adhesion molecules. Moreover, the expression of SNHG5 was shown to be correlated with epithelial-mesenchymal transition (EMT) markers in western blots and immunofluorescence. SNHG5 also had significant effects of antimigration and anti-invasion on LAD cells in vitro. Furthermore, the migration and invasion of A549 cells were suppressed by overexpressed SNHG5 in the EMT progress induced by transforming growth factor β1 (TGF-β1), and this might be due to the inhibition of the expression of EMT-associated transcription factors involving Snail, SLUG, and ZEB1. In LAD tissues, the expression of SNHG5 exhibited a positive association with E-cadherin protein expression but a negative correlation with N-cadherin and vimentin, according to the results of quantitative real-time PCR (qRT-PCR). In summary, the current work demonstrated that the lncRNA SNHG5 might limit cell migration and invasion of LAD cancer via decreasing the EMT process, indicating that SNHG5 might be used as a target for LAD therapeutic methods.

Downregulation of LncRNA SNHG7 Sensitizes Colorectal Cancer Cells to Resist Anlotinib by Regulating miR-181a-5p/GATA6.

Long noncoding RNAs are a novel class of regulators in human cancers. It has been reported that small nucleolar RNA hostgene 7 (SNHG7) can sponge microRNAs to regulate colorectal cancer (CRC) progression. Given its important regulatory role in cancer biology, we wondered whether SNHG7 is involved in drug resistance to anlotinib (ATB) in CRC. To answer this, we quantified the expression of SNHG7 by quantitative real-time PCR. We performed the Cell Counting Kit-8 and Colony formation assay, flow cytometric analysis, RNA pull-down, RNA-binding protein immunoprecipitation assay, and Luciferase reporter assay to confirm the interaction among SNHG7, miR-181a-5p, and GATA6. We found that SNHG7 was significantly upregulated in CRC tissues and cell lines and ATB-resistant cell lines, which was closely related to the poor overall survival of patients. Loss-of-function studies demonstrated that SNHG7 knockdown can inhibit CRC cell proliferation, increase apoptosis, and sensitize CRC cells to resist ATB. Mechanistic studies showed that SNHG7 acted as a competitive endogenous RNA to sponge miR-181a-5p to regulate the expression of GATA6, thereby promoting ATB resistance in ATB-resistant cell lines. In conclusion, SNHG7 plays an important role in ATB resistance, and it may be used to monitor ATB resistance in CRC.

Long Non-Coding RNA SNHG4 Expression in Women with Endometriosis: A Pilot Study.

Endometriosis is a chronic disease of the genital organs that mainly affects women of reproductive age. The analysis of long non-coding RNA (lncRNA) in endometriosis is a novel field of science. Recently, attention has been drawn to SNHG4, which is incorrectly expressed in various human diseases, including endometriosis. The aim of this pilot study was to analyze the expression of lncRNA small nucleolar RNA host gene 4 (SNHG4) and to investigate its significance in endometriosis. LncRNA SNHG4 expression was investigated in paraffin blocks in endometriosis patients (n = 100) and in endometriosis-free controls (n = 100) using a real-time PCR assay. This study revealed a higher expression of SNHG4 in endometriosis patients than in controls. A statistically significant relationship between expression level and SNHG4 was found in relation to The Revised American Society for Reproductive Medicine classification of endometriosis, 1996, in the group of patients with endometriosis. This pilot study has revealed that gene expression in SNHG4 plays an important role in the pathogenesis of endometriosis.

Molecular Mechanism of Long Noncoding RNA SNHG14 in Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells through the NEDD4L/FOXA2/PCP4 Axis.

Bone marrow-derived mesenchymal stem cells (BMSCs) have a superior potential of osteogenic differentiation (OD) and a promising stem cell type to treat bone defects. This study sought to investigate the molecular mechanism of long noncoding RNA small nucleolar RNA host gene 14 (SNHG14) in OD of BMSCs. Western blot analysis or RT-qPCR showed that SNHG14, neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), and Purkinje cell protein 4 (PCP4) were upregulated whereas forkhead box A2 (FOXA2) was declined in OD of BMSCs. RT-qPCR and cell staining showed that SNHG14 downregulation repressed OD of BMSCs, as manifested by reductions in osteopontin and osteocalcin levels, the mineralization degree, and alkaline phosphatase activity. RNA/Co/chromatin immunoprecipitation and dual-luciferase assays and determination of mRNA stability and ubiquitination level showed that SNHG14 bound to human antigen R improves NEDD4L mRNA stability and expression, further promoted FOXA2 ubiquitination to inhibit FOXA2 expression, and then reduced FOXA2 enrichment on the PCP4 promoter to upregulate PCP4 transcription. Functional rescue experiments showed that the overexpression of NEDD4L or PCP4 and knockdown of FOXA2 both attenuated the inhibition of SNHG14 downregulation on OD of BMSCs. Overall, our findings suggested that SNHG14 promoted OD of BMSCs through the NEDD4L/FOXA2/PCP4 axis.

The study of long noncoding RNA SNHG5 and PANDAR genes expression in newly diagnosed egyptian adult acute myeloid leukemia patients

BACKGROUND: Due to their impact on crucial steps in hematopoiesis, long noncoding RNAs (lncRNAs) deregulation potentially accelerates the growth and development of blood cancers like acute myeloid leukemia (AML). The study aimed to look into different expression patterns, prognostic value, and clinical importance of lncRNA small nucleolar RNA host gene 5 (SNHG5) and promoter of cyclin-dependent kinase inhibitor 1A antisense DNA damage-activated RNA (PANDAR) genes in Egyptian adult patients with AML. SUBJECTS AND METHODS: The case–control study was conducted between 2019 and 2022 at the Clinical Pathology Department at the National Cancer Institute, Cairo University, Egypt. The study involved 80 recently diagnosed patients with AML and 20 healthy controls. Real-time quantitative reverse transcription polymerase chain reaction was used to assess the levels of expression of SNHG5 and PANDAR genes. RESULTS: In comparison to healthy controls, there was a significantly higher SNHG5 gene expression (P = 0.026) and PANDAR expression (P &lt; 0.001) in patients’ bone marrow samples. The study of the correlations revealed a significant positive association between SNHG5 and PANDAR genes in AML patients. The overall survival (OS) was significantly better in the low SNHG5 gene expression group than in the high SNHG5 gene expression group. No significant difference was detected regarding the disease-free survival (DFS) between patients with low expression and high expression of the SNHG5 gene. No significant variation between high PANDAR gene and low PANDAR gene expression regarding OS and DFS. CONCLUSION: SNHG5 and PANDAR may have a pathogenic role in AML, and their overexpression might be considered a marker for diagnosis in AML patients in Egypt. SNHG5 expression can be used as a predictor for OS, while PANDAR expression cannot be used as a predictor for OS or DFS in patients.

METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis

Accumulating evidence indicates that m6A methyltransferase 3 (METTL3) plays a pivotal role in different malignancies including melanoma. However, the function and underlying mechanisms by which METTL3 contributes to the tumorigenesis of melanoma remain undocumented. The association of METTL3 and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) with clinicopathological characteristics and prognosis in patients with melanoma was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and The Cancer Genome Atlas data sets. The role of METTL3 in melanoma cells was assessed by in vitro and in vivo experiments. The m6A dot blot, methylated RNA immunoprecipitation (MeRIP), and RT-qPCR were used to verify METTL3-mediated m6A modification of lncRNA SNHG3. The effect of METTL3 on lncRNA SNHG3 was determined by luciferase gene reporter assay, RT-qPCR, and Western blotting. We found that METTL3 was upregulated in melanoma tissue samples and associated with poor survival in patients with melanoma. Knockdown of METTL3 suppressed the growth and invasion of melanoma cells in vitro and in vivo, whereas restored expression of METTL3 promoted these effects. Mechanistic investigations showed that knockdown of METTL3 reduced SNHG3 m6A levels and its messenger ribonucleic acid (mRNA) expression levels. SNHG3 could act as a sponge of microRNA (miR)-330-5p to upregulate the expression of CCHC-type zinc finger nucleic acid binding protein (CNBP). SNHG3 overexpression reversed METTL3-knockdown-caused antitumor effects, miR-330-5p upregulation and CNBP downregulation. SNHG3 had a positive correlation with METTL3 expression but a negative correlation with miR-330-5p expression in melanoma tissue samples. In conclusion, our findings demonstrated that METTL3-mediated m6A modification of lncRNA SNHG3 promoted the growth and invasion of melanoma cells by regulating the miR-330-5p/CNBP axis.

Long non‑coding RNA SNHG5 promotes osteogenic differentiation of human periodontal ligament stem cells via mediating miR‑23b‑3p/Runx2 axis.

The treatment of bone loss due to periodontitis has posed a great challenge for physicians for decades. Therefore, it is of extraordinary significance to identify an effective regeneration scheme for alveolar bone. This study aimed to investigate long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) whether sponges microRNA-23b-3p (miR-23b-3p) to achieve the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Results revealed that the expression of SNHG5 was upregulated whereas that of miR-23b-3p was downregulated in osteogenic hPDLSCs. Alizarin red staining assays and qRT-PCR demonstrated that SNHG5 silencing or miR-23b-3p overexpression inhibits hPDLSCs osteogenic differentiation and vice versa. In addition, miR-23b-3p partially abolished the promotive effect of SNHG5 on osteogenic differentiation of hPDLSCs. Dual luciferase report and RNA pulldown assay verified that miR-23b-3p is a regulatory target of SNHG5 and that Runx2 is a gene target of miR-23b-3p. In brief, the results demonstrate that SNHG5 promotes the osteogenic differentiation of hPDLSCs by regulating the miR-23b-3p/Runx2 axis. Our study provides novel mechanistic insights into the critical role of lncRNA SNHG5 as a miR-23b-3p sponge to regulate Runx2 expression in hPDLSCs and may serve as a potential therapeutics target for periodontitis.

Alternative Splicing of lncRNAs From SNHG Family Alters snoRNA Expression and Induces Chemoresistance in Hepatoblastoma

Hepatoblastoma (HB) is a common pediatric malignant liver tumor that is characterized by a low level of genetic mutations. Alternative splicing (AS) has been shown to be closely associated with cancer progression, especially in tumors with a low mutational burden. However, the role of AS in HB remains unknown. Transcriptome sequencing was performed on 5 pairs of HB tissues and matched non-tumor tissues to delineate the AS landscape in HB. AS events were validated in 92 samples from 46 patients. RNA pull-down and RNA immunoprecipitation assays were carried out to identify splicing factors that regulate the AS of small nucleolar RNA host genes (SNHG). Patient-derived organoids (PDOs) were established to investigate the role of the splicing factor polyadenylate-binding nuclear protein 1 (PABPN1). This study uncovered aberrant alternative splicing in HB, including lncRNAs from SNHG family that undergo intron retention in HB. Further investigations revealed that PABPN1, a significantly upregulated RNA binding protein, interacts with splicing machinery in HB, inducing the intron retention of these SNHG RNAs and the downregulation of intronic small nucleolar RNAs (snoRNAs). Functionally, PABPN1 acts as an oncofetal splicing regulator in HB by promoting cell proliferation and DNA damage repair via inducing the intron retention of SNHG19. Knock-down of PABPN1 increases the cisplatin sensitivity of HB PDOs. Our findings revealed the role of intron retention in regulating snoRNA expression in hepatoblastoma, explained detailed regulatory mechanism between PABPN1 and the intron retention of SNHG RNAs, and provided insight into the development of new HB treatment options.

GATA-binding protein 4 promotes neuroinflammation and cognitive impairment in Aβ1-42 fibril-infused rats through small nucleolar RNA host gene 1/miR-361-3p axis.

Aging with dysregulated metabolic and immune homeostasis stimulates pyroptosis, neuroinflammation, and cellular senescence, thus contributing to etiopathogenesis of Alzheimer's disease. GATA-binding protein 4 (GATA4) functions as a transcriptional factor in response to DNA damage, and is associated with neuroinflammation and cellular senescence. The role of GATA4 in Alzheimer's disease was investigated. GATA4 was elevated in hippocampus of Aβ1-42 fibril-infused rats. Injection with shRNA targeting GATA4 reduced escape latency with increase of time in target quadrant and number of platform crossings in Aβ1-42 fibril-infused rats. Moreover, knockdown of GATA4 ameliorated morphological changes of hippocampus and reduced amyloid plaque deposition in Aβ1-42 fibril-infused rats. Silence of GATA4 repressed neuroinflammation and apoptosis in Aβ1-42 fibril-infused rats. Loss of GATA4 in Aβ1-42 fibril-infused rats reduced the expression of specificity protein 1 (Sp1) to downregulate long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) and upregulated miR-361-3p. Loss of SNHG1 ameliorated learning and memory impairments in Aβ1-42 fibril-infused rats. Overexpression of Sp1 attenuated GATA4 silence-induced decrease of escape latency, increase of time in target quadrant, and number of platform crossings in Aβ1-42 fibril-infused rats. In conclusion, silence of GATA4 ameliorated cognitive dysfunction and inhibited hippocampal inflammation and cell apoptosis through regulation of Sp1/SNHG1/miR-361-3p.

Small nucleolar RNA host gene 25 is a long non-coding RNA helps diagnose and predict outcomes in prostate cancer

BackgroundThe role of a long non-coding RNA called small nucleolar RNA host gene 25 (SNHG25) has been studied in some tumor types but the correlation between SNHG25 and PCA remains unknown. MethodsThe relationship between clinicopathologic characteristics and SNHG25 expression was evaluated using The Cancer Genome Atlas data. The binary classifier value of SNHG25 was calculated using areas under receiver operating characteristic (ROC) curves. Outcomes were evaluated using Kaplan-Meier and Cox regression analyses. Gene set enrichment was performed to identify potential SNHG25 functions. ResultsSNHG25 expression was significantly increased in PCA and correlated with age, primary therapy outcome, N stage, Gleason score, and residual tumor (p < 0.05). ROC curves demonstrated the effect of SNHG25 on diagnosis and outcomes (area under the curve = 0.923). Higher SNHG25 expression predicted shorter progression-free interval (PFI) (p < 0.001), and Cox regression showed that SNHG25 expression was an independent risk factor for reduced PFI (p = 0.028). SNHG25 expression was associated with mRNA and protein metabolism. ConclusionsSNHG25 expression increases significantly in PCA and is negatively associated with PFI. It is a potential diagnostic and prognostic biomarker in PCA.