SNHG16/miR-205/HDAC5 is involved in the progression of renal fibrosis.

Renal interstitial fibrosis (RIF) represents an irreversible and progressive pathological manifestation of chronic renal disease, which ultimately leads to end-stage renal disease. Long noncoding RNAs (lncRNAs) have been suggested to be involved in the progression of RIF. Small nucleolar RNA host gene 16 (SNHG16), a member of lncRNAs, has been found to be involved in the progression of pulmonary fibrosis. This paper first researched the effect of SNHG16 on renal fibrosis. We established a unilateral ureteral obstruction (UUO)-induced mouse RIF model by ligation of the left ureter to evaluate the biological function of SNHG16 in RIF. As a result, SNHG16 was upregulated in UUO-induced renal fibrotic tissues. Knockdown of SNHG16 inhibited RIF and reduced alpha-smooth muscle actin (α-SMA), fibronectin, and college IV expression. miR-205 was a target of SNHG16, and downregulated in UUO-induced renal fibrotic tissues. Inhibition of miR-205 promoted RIF and increased the expression of α-SMA, college IV, and fibronectin. Overexpression of SNHG16 promoted the UUO-induced RIF, but miR-205 abrogated this effect of SNHG16. Histone deacetylase 5 (HDAC5) showed high expression in UUO-induced renal fibrotic tissues. Knockdown of HDAC5 significantly reduced α-SMA, fibronectin, and college IV expression in renal tissues of UUO-induced mice. Inhibition of miR-205 promoted HDAC5 expression, but knockdown of SNHG16 inhibited HDAC5 expression in renal tissues of UUO-induced mice. In conclusion, SHNG16 is highly expressed in renal fibrotic tissues of UUO-induced mice. Knockdown of SHNG16 may prevent UUO-induced RIF by indirectly upregulating HDAC5 via targeting miR-205. SHNG16 may be novel target for treating renal fibrosis.

Long noncoding RNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in alveolar hemorrhage associated with systemic lupus erythematosus.

BACKGROUND: Dysregulated long noncoding RNA (lncRNA) expression with increased apoptosis has been demonstrated in systemic lupus erythematosus (SLE) patients with alveolar hemorrhage (AH). SNHG16, a lncRNA, can enhance pulmonary inflammation by sponging microRNAs, and upregulate toll-like receptor 4 (TLR4) expression via stabilizing its mRNAs. TRAF6, a TLR4 downstream signal transducer, can induce autophagy and NETosis formation. In this study, we investigated whether SNHG16 could regulate TLR4-mediated autophagy and NETosis formation in SLE-associated AH. METHODS: Expression of SNHG16, TLR4 and TRAF6 and cell death processes were examined in lung tissues and peripheral blood (PB) leukocytes from AH patients associated with SLE and other autoimmune diseases, and in the lungs and spleen from a pristane-induced C57BL/6 mouse AH model. SNHG16-overexpressed or -silenced alveolar and myelocytic cells were stimulated with lipopolysaccharide (LPS), a TLR4 agonist, for analyzing autophagy and NETosis, respectively. Pristane-injected mice received the intra-pulmonary delivery of lentivirus (LV)-SNHG16 for overexpression and prophylactic/therapeutic infusion of short hairpin RNA (shRNA) targeting SNHG16 to evaluate the effects on AH. Renal SNHG16 expression was also examined in lupus nephritis (LN) patients and a pristane-induced BALB/c mouse LN model. RESULTS: Up-regulated SNHG16, TLR4 and TRAF6 expression with increased autophagy and NETosis was demonstrated in the SLE-AH lungs. In such patients, up-regulated SNHG16, TLR4 and TRAF6 expression was found in PB mononuclear cells with increased autophagy and in PB neutrophils with increased NETosis. There were up-regulated TLR4 expression and increased LPS-induced autophagy and NETosis in SNHG16-overexpressed cells, while down-regulated TLR4 expression and decreased LPS-induced autophagy and NETosis in SNHG16-silenced cells. Pristane-injected lung tissues had up-regulated SNHG16, TLR4/TRAF6 levels and increased in situ autophagy and NETosis formation. Intra-pulmonary LV-SNHG16 delivery enhanced AH through up-regulating TLR4/TRAF6 expression with increased cell death processes, while intra-pulmonary prophylactic and early therapeutic sh-SNHG16 delivery suppressed AH by down-regulating TLR4/TRAF6 expression with reduced such processes. In addition, there was decreased renal SNHG16 expression in LN patients and mice. CONCLUSIONS: Our results demonstrate that lncRNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in the human and mouse AH lungs, and provide a therapeutic potential of intra-pulmonary delivery of shRNA targeting SNHG16 in this SLE-related lethal manifestation.

PCSK9 inhibitor attenuates atherosclerosis by regulating SNHG16/EZH2/TRAF5-mediated VSMC proliferation, migration, and foam cell formation.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has been demonstrated to exert a great cardioprotection in cardiometabolic impairments, including atherosclerosis. However, its underlying mechanism remains not fully understood. This study focuses on uncovering the actions of PCSK9 inhibitor on the connection between atherosclerosis and vascular smooth muscle cell (VSMC) behaviors. qRT-PCR was utilized to detect the expression of SNHG16. Proliferation and migration of VSMC were characterized by Cell Counting Kit-8 and wound healing assays. The intracellular lipids and foam cell formation were assessed by Oil Red O staining, fluorescence image, and cholesterol quantification kit. Atherosclerosis in vivo was evaluated by imaging the atherosclerotic lesions, hematoxylin-eosin staining, Oil Red O staining and Masson staining. The interaction between SNHG16 with EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) were investigated by fluorescence in situ hybridization, RNA immunoprecipitation, and chromatin immunoprecipitation assays. A ApoE-/- mice model was used to validate the role of PCSK9 inhibitor and SNHG16 for atherosclerosis. The protective regulation of PCSK9 inhibitor was observed both in high-fat diet (HFD)-fed mice and oxidized low-density lipoprotein (ox-LDL)-treated VSMC, as manifested in the decreased the atherosclerotic lesions in vivo, as well as the weakened cell proliferation, migration, and formation of foam cells in vitro. SNHG16 was identified to be a downstream effector of PCSK9 inhibitor-mediated biological functions, of which knockdown also significantly ox-LDL-treated VSMC proliferation, migration, and foam cell formation abilities. SNHG16 epigenetically suppressed TRAF5 via recruiting EZH2. Silencing of TRAF5 abolished the protective effects of SNHG16 knockdown on the pathogenesis of atherosclerosis. Collectively, PCSK9 inhibitor attenuated atherosclerosis by regulating SNHG16/EZH2/TRAF5 axis to impair the proliferation, migration, and foam cell formation of VSMC.

The value of urinary exosomal lncRNA SNHG16 as a diagnostic biomarker for bladder cancer.

OBJECTIVE: To detect the expression level of urinary exosomal lncRNA SNHG16 in patients with bladder cancer and healthy individuals and explore its clinical application value in the diagnosis of bladder cancer. METHODS: Urine samples were collected from 42 patients with bladder cancer and 42 healthy volunteers who visited Lu'an Hospital of Anhui Medical University and the Second Hospital of Tianjin Medical University from January 2020 to December 2022. The expression levels of lncRNA SNHG16 in urinary exosomes of the two groups were detected by RT‒qPCR, and their correlation with clinical pathological parameters of bladder cancer patients was analysed. An Receiver Operating Characteristic(ROC) curve was drawn to analyse the diagnostic value of urinary exosomal lncRNA SNHG16 for bladder cancer and compared with urinary cytology. RESULTS: The expression of urinary exosomal lncRNA SNHG16 in patients with bladder cancer was significantly higher (P < 0.05), and the expression level had no correlation with the age, sex, pathological T stage, pathological grade, or tumour size of bladder cancer patients (P > 0.05). The Area Under Curve(AUC) of urinary exosomal lncRNA SNHG16 in diagnosing bladder cancer was 0.791, which was superior to that of urinary cytology (AUC = 0.597). CONCLUSION: Urinary exosomal lncRNA SNHG16 with high expression can serve as a potential diagnostic biological marker for bladder cancer.

CTCF-activated SNHG16 facilitates gastrointestinal stromal tumor by targeting miR-128-3p/CASC3 axis.

In this study, it was ascertained that SNHG16 was up-regulated in gastrointestinal stromal tumor (GIST) tissues and cells, and was responsible for the aggravated malignant behaviors of GIST cells. CTCF served as a transcription activator responsible for the overexpression of SNHG16 in GIST cells. MiR-128-3p was negatively regulated by SNHG16 and exerted anti-tumor effects. Moreover, CASC3 was the direct target mRNA of miR-128-3p, through which miR-128-3p exerted function influence on GIST cell malignant behaviors. SNHG16 competitively bound with miR-128-3p against CASC3, thus positively regulating CASC3 expression. Finally, functional assays carried out in vitro proved SNHG16 could modulate GIST cell proliferation, migration, invasion and apoptosis via miR-128-3p/CASC3 axis. Animal experiments were also designed and implemented in a rescue way and evidenced that up-regulation of CASC3 countervailed the inhibitory impacts of SNHG16 silence on the progression of GIST. In summary, SNHG16 up-regulated by CTCF facilitated the progression of GIST through miR-128-3p/CASC3.

LncRNA SNHG16 Knockdown Promotes Diabetic Foot Ulcer Wound Healing via Sponging MiR-31-5p.

Diabetic foot ulcers are caused by nerve abnormalities and vascular lesions in the distal lower limbs of diabetic patients. However, the causes of diabetic foot ulcers are diverse and the treatment process is complex. Therefore, understanding the pathogenesis of diabetic foot ulcers through lncRNA and formulating effective means are the key to the cure of patients. Tissues were collected from 76 diabetic foot ulcer patients and 50 non-diabetic patients undergoing traumatic amputation. Human dermal fibroblasts (HDFs) were induced by high glucose to obtain diabetic foot ulcer cell model. The lncRNA SNHG16 (SNHG16) and miR-31-5p expression in tissues and cells was detected by real-time quantitative reverse transcription PCR (RT-qPCR). Cell Counting Kit-8 (CCK-8) and Transwell assays were used to evaluate the biological behavior of the cells, and the association between SNHG16 and miR-31-5p was explored by luciferase reporting assay. SNHG16 was distinctly expressed in diabetic foot ulcer tissue samples, while miR-31-5p was decreased. In vitro cell function assays confirmed that the proliferation level was inhibited in the constructed diabetic foot ulcer cell model (HG group), as was the migration and invasion ability. After transfection with silencing SNHG16, the biological behavior of the cells was promoted. Mechanistically, SNHG16 sponge miR-31-5p regulated disease progression. Recovery experiments revealed that miR-31-5p inhibitor counteracted the effect of silencing SNHG16 on cell viability. SNHG16 knockdown may regulate the biological function of cells by targeting miR-31-5p to promote wound healing and ameliorate the condition of diabetic foot ulcer patients.

Expression analysis of vitamin D receptor and its related long non-coding RNAs in peripheral blood of patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurological condition that is associated with abnormal expression of several transcripts. Vitamin D receptor (VDR) is a possible participant in the pathogenesis of PD. METHODS AND RESULTS: In the present research project, we evaluated expressions of VDR and three functionally associated long non-coding RNAs with this signaling, namely SNHG6, SNHG16 and LINC00346 in PD patients versus normal controls. Level of SNHG6 transcripts was lower in total patients in comparison with total controls (Expression ratio (95% CI) 0.44 (0.17-1.08)) and in male patients compared with male controls (Expression ratio (95% CI) 0.29 (0.13-0.65)). On the other hand, expression of VDR was higher in total patients compared with total controls (Expression ratio (95% CI) 10.86 (4.37-26.72)) and in male patients compared with male controls (Expression ratio (95% CI) 22.16 (6.23-78.8)). There was no significant difference in expression of SNHG16 and LINC00346 between PD patients and controls. Amounts of SNHG6 and VDR transcripts could differentiate total PD patients from total controls with AUC values of 0.66 and 0.86, respectively. CONCLUSIONS: Cumulatively, the results of the present investigation imply dysregulation of VDR signaling in PD and necessitate conduction of further functional studies.

LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability.

BACKGROUND: Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling. RESULTS: One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells. CONCLUSIONS: The newly identified SNHG16-EIF4A3-RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.

Downregulation of lncRNA SNHG16 inhibits vascular smooth muscle cell proliferation and migration in cerebral atherosclerosis by targeting the miR-30c-5p/SDC2 axis.

Atherosclerosis (AS) is the basic lesion underlying the occurrence and development of cerebrovascular diseases. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in AS. We aimed to explore the role of SNHG16 in AS and the molecular mechanism of VSMC involvement in the regulation of AS. The expression levels of SNHG16, miR-30c-5p and SDC2 were detected by qRT-PCR. CCK-8, wound healing and Transwell assays were used to assess ox-LDL-induced VSMC proliferation, migration, and invasion, respectively. Western blot analysis was used to detect SDC2 and MEK/ERK pathway-related protein levels. A dual-luciferase reporter assay confirmed the binding of SNHG16 with miR-30c-5p and miR-30c-5p with SDC2. SNHG16 and SDC2 expression was upregulated in patients with AS and ox-LDL-induced VSMCs, while miR-30c-5p was downregulated. Ox-LDL-induced VSMC proliferation and migration were increased, and the MEK/ERK signalling pathway was activated. MiR-30c-5p was targeted to SNHG16 and SDC2. Downregulating SNHG16 or upregulating miR-30c-5p inhibited ox-LDL-induced VSMC proliferation and migration and inhibited MEK/ERK signalling pathway activation. In contrast, downregulating miR-30c-5p or upregulating SDC2 reversed the effects of downregulating SNHG16 or upregulating miR-30c-5p. Furthermore, downregulating SDC2 inhibited ox-LDL-induced proliferation and migration of VSMCs and inhibited activation of the MEK/ERK signalling pathway, while upregulating lncRNA SNHG16 reversed the effects of downregulating SDC2. Downregulation of SNHG16 inhibited VSMC proliferation and migration in AS by targeting the miR-30c-5p/SDC2 axis. This study provides a possible therapeutic approach to AS.

Correlation of small nucleolar RNA host gene 16 with acute respiratory distress syndrome occurrence and prognosis in sepsis patients.

BACKGROUND: Long noncoding RNA small nucleolar RNA host gene 16 (lnc-SNHG16) regulates sepsis-induced acute lung injury and inflammation, which is involved in the pathophysiology of acute respiratory distress syndrome (ARDS). The present study intended to explore the role of lnc-SNHG16 as a potential biomarker indicating ARDS risk, disease severity, inflammation, and mortality in sepsis. METHODS: Peripheral blood mononuclear cell (PBMC) samples were collected from 160 sepsis patients within 24 hours after admission and 30 healthy controls (HCs). Then, lnc-SNHG16 in PBMCs was detected by reverse transcription-quantitative polymerase chain reaction. Sepsis patients were followed up until death or up to 28 days. RESULTS: lnc-SNHG16 was declined in sepsis patients compared with HCs (p < 0.001). The incidence of ARDS was 27.5% among sepsis patients; meanwhile, sepsis patients with ARDS had higher mortality than those without ARDS (p < 0.001). Furthermore, lnc-SNHG16 was declined in sepsis patients with ARDS compared to those without ARDS (p < 0.001); besides, higher lnc-SNHG16 was independently correlated with declined ARDS occurrence in sepsis patients (p = 0.001), while primary respiratory infection and higher CRP were independently correlated with elevated ARDS occurrence in sepsis patients (both p < 0.05). Moreover, a negative correlation was found in lnc-SNHG16 with history of diabetes, history of chronic obstructive pulmonary disease, and APACHE II and SOFA scores (all p < 0.05). Additionally, lnc-SNHG16 was declined in sepsis deaths compared with survivors (p = 0.002), while it was not independently linked with sepsis mortality. CONCLUSION: lnc-SNHG16 correlates with lower ARDS occurrence and better prognosis in sepsis patients.

SNHG16 promotes hepatocellular carcinoma development via activating ECM receptor interaction pathway.

BACKGROUND: Accumulating data have suggested that long non-coding RNAs (lncRNAs) play important roles in regulating tumor cell growth. This study was designed to investigate the role of SNHG16 in hepatocellular carcinoma (HCC). METHODS: SNHG16 expression was detected with real-time polymerase chain reaction (PCR). The cutoff value of SNHG16 for tumor-free survival (TFS) was determined with receiver operating characteristic curve analysis. Small interfering RNA was used to inhibit the expression of SNHG16 in HCC cell lines. The biologic behavior of HCC cell was determined with cell viability assay and Transwell assay in vitro. The potential predictive value of SNHG16 on prognosis was analyzed by Kaplan-Meier curves and Cox proportional hazards regression model. RESULTS: SNHG16 expression was upregulated in tumor tissues and HCC cell lines. High expression of SNHG16 was associated with tumor recurrence and poor prognosis after surgery. Multivariate analysis revealed that SNHG16 was an independent prognostic factor for poor recurrence-free survival. Moreover, inhibition of SNHG16 in HepG2, Hep3B, and BEL-7402 cells significantly reduced cell invasiveness and proliferation. Mechanistic analyses indicated that the ECM-receptor interaction pathway was remarkably activated by SNHG16. CONCLUSIONS: SNHG16 might be a promising biomarker for predicting tumor recurrence in HCC patients after surgery and a potential therapeutic target for HCC.

SNHG16/miR-485-5p/BMP7 axis modulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.

BACKGROUND: Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is crucial for bone formation and its dysfunction is reported to be linked to osteoporosis (OP). The present study aimed to probe the function of the long non-coding RNA small nucleolar RNA host gene 16 (SNHG16) with respect to modulating the osteogenic differentiation of hBMSCs. METHODS: SNHG16 expression in hBMSCs obtained from OP patients was measured by a quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function and loss-of-function models of SNHG16 were established with hBMSCs. The expression of OP-related genes (ALP, OCN and OPN) in hBMSCs was determined by qRT-PCR and western blotting. StarBase, TargetScan7.2, miRDB and PicTar databases were used to predict the binding sites between SNHG16 and miR-485-5p, miR-485-5p and 3'-UTR of bone morphogenetic protein 7 (BMP7), respectively. A dual-luciferase reporter assay was used to determine the regulatory relationships between SNHG16 and miR-485-5p, miR-485-5p and 3'-UTR of BMP7, respectively. RESULTS: SNHG16 was remarkably down-regulated in hBMSCs obtained from patients with OP. Overexpression of SNHG16 promoted the osteogenic differentiation of hBMSCs, whereas knockdown of SNHG16 suppressed it. Mechanistically, miR-485-5p is a target of SNHG16, and miR-485-5p can reverse the function of SNHG16. BMP7 is also identified as a target of miR-485-5p and can be indirectly modulated by SNHG16 in hBMSCs. CONCLUSIONS: SNHG16 promotes the osteogenic differentiation of hBMSCs via regulating the miR-485-5p/BMP7 axis and comprises a prospective therapy target for OP.

LncRNA SNHG16 contributes to tumor progression via the miR-302b-3p/SLC2A4 axis in pancreatic adenocarcinoma.

BACKGROUND: It has been reported that the lncRNA SNHG16 has significantly increased expression in pancreatic adenocarcinoma (PC). However, the functions and mechanisms of SNHG16 are not clear. The aim of this study was to explore the effects of SNHG16 on PC. METHODS: qRT-PCR analysis was applied to detect the expression levels of SNHG16, miR-302b-3p and SLC2A4 in PC tissues and cells. CCK8 and EdU assays were used to evaluate the proliferation of PC cells. Transwell assays were used to assess PC cell migration and invasion. Apoptosis was evaluated by flow cytometry, and the expression of apoptosis-related proteins (including Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9) was tested by western blotting. The interactions between miR-302b-3p and SNHG16 or miR-302b-3p and the 3'UTR of SLC2A4 mRNA were clarified by a dual luciferase reporter assay and RNA immunoprecipitation. RESULTS: SNHG16 expression was significantly elevated in PC tissues and cell lines and was associated with poor prognosis of PC patients. Knockdown of SNHG16 reduced PC cell proliferation, migration and invasion. SNHG16 acted as a sponge to regulate miR-302b-3p expression in PC cells. In addition, miR-302b-3p targeted SLC2A4 directly. CONCLUSIONS: SNHG16 promoted the progression of PC via the miR-302b-3p/SLC2A4 axis and was expected to be a potential target for the early diagnosis and treatment of PC.

LncRNA SNHG16 promotes pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung diseases with a poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to be involved in IPF in several studies. However, the role of lncRNA SNHG16 in IPF is largely unknown. METHODS: Firstly, experimental pulmonary fibrosis model was established by using bleomycin (BML). Histology and Western blotting assays were used to determine the different stages of fibrosis and expression of several fibrosis biomarkers. The expression of SNHG16 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). EdU staining and wound-healing assay were utilized to analyze proliferation and migration of lung fibroblast cells. Molecular mechanism of SNHG16 was explored by bioinformatics, dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and qRT-PCR. RESULTS: The expression of SNHG16 was significantly up-regulated in bleomycin-(BLM) induced lung fibrosis and transforming growth factor-ß (TGF-ß)-induced fibroblast. Knockdown of SNHG16 could attenuate fibrogenesis. Mechanistically, SNHG16 was able to bind and regulate the expression of miR-455-3p. Moreover, SNHG16 also regulated the expression of Notch2 by targeting miR-455-3p. Finally, SNHG16 could promote fibrogenesis by regulating the expression of Notch2. CONCLUSION: Taken together, our study demonstrated that SNHG16 promoted pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway. These findings might provide a novel insight into pathologic process of lung fibrosis and may provide prevention strategies in the future.

Evaluation of expression of VDR-associated lncRNAs in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been shown to cause serious health problems among them is the Acute Respiratory Distress syndrome (ARDS). Vitamin D receptor (VDR) signaling possibly partakes in the pathophysiology of this devastating complication. METHODS: In the current project, we have appraised expression levels of VDR, CYP27B1 and a number of associated lncRNAs in the circulation of COVID-19 patients versus healthy subjects using real-time PCR method. RESULTS: Expression of SNHG6 was considerably lower in COVID-19 patients compared with control subjects (Ratio of mean expression (RME) = 0.22, P value = 7.04E-05) and in both female and male COVID-19 patients compared with sex-matched unaffected individuals (RME = 0.32, P value = 0.04 and RME = 0.16, P value = 0.000679683, respectively). However, its expression was similar among ICU-hospitalized and non-ICU patients. Similarly, expression of SNHG16 was lower in in COVID-19 patients compared with controls (RME = 0.20, P value = 5.94E-05) and in both female and male patients compared with sex-matched controls (RME = 0.32, P value = 0.04 and RME = 0.14, P value = 0.000496435, respectively) with no significant difference among ICU-hospitalized and non-ICU hospitalized patients. Expression of VDR was lower in COVID-19 patients compared with controls (RME = 0.42, P value = 0.04) and in male patients compared with male controls (RME = 0.27, P value = 0.02). Yet, expression of VDR was statistically similar between female subgroups and between ICU-hospitalized and non-ICU hospitalized patients. Expression levels CYP27B, Linc00511 and Linc00346 were similar among COVID-19 patients and healthy subjects or between their subgroups. Significant correlations have been detected between expression levels of VDR, CYP27B and SNHG6, SNHG16, Linc00511 and Linc00346 lncRNAs both among COVID-19 patients and among healthy controls with the most significant ones being SNHG6 and SNHG16 (r = 0.74, P value = 3.26e-17 and r = 0.81, P = 1.54e-22, respectively). CONCLUSION: Combination of transcript levels of VDR, CYP27B and SNHG6, SNHG16, Linc00511 and Linc00346 could differentiate patients from controls with AUC = 0.76, sensitivity = 0.62 and specificity = 0.81. The current data potentiate SNHG6, SNHG16 and VDR as possible contributors in COVID-19 infection but not in the severity of ARDS.

LncRNA small nucleolar RNA host gene 16 (SNHG16) silencing protects lipopolysaccharide (LPS)-induced cell injury in human lung fibroblasts WI-38 through acting as miR-141-3p sponge.

Long noncoding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) is correlated with cell injuries, including pneumonia. However, its role and mechanism remain vague in pneumonia. The interplay among genes was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. SNHG16 and sushi domain containing 2 (SUSD2) were upregulated, and miRNA (miR)-141-3p was downregulated in the serum of acute pneumonia patients and lipopolysaccharide (LPS)-challenged human lung fibroblasts WI-38. LPS induced apoptosis, autophagy, and inflammatory response in WI-38 cells, which was significantly attenuated by SNHG16 knockdown and/or miR-141-3p overexpression. Notably, both SNHG16 and SUSD2 were identified as target genes of miR-141-3p. Besides, the suppressive role of SNHG16 knockdown in LPS-induced in WI-38 cells was partially abolished by miR-141-3p silencing, and the similar inhibition of miR-141-3p overexpression was further blocked by SUSD2 restoration. In conclusion, knockdown of SNHG16 could alleviate LPS-induced apoptosis, autophagy, and inflammation in WI-38 cells partially though the SNHG16/miR-141-3p/SUSD2 pathway.

Down-regulation of SNHG16 alleviates the acute lung injury in sepsis rats through miR-128-3p/HMGB3 axis.

BACKGROUND: Long noncoding RNAs contribute to various inflammatory diseases, including sepsis. We explore the role of small nucleolar RNA host gene 16 (SNHG16) in sepsis-mediated acute lung injury (ALI) and inflammation. METHODS: A sepsis-induced ALI rat model was constructed by the cecal ligation and perforation method. The profiles of SNHG16, miR-128-3p, and high-mobility group box 3 (HMGB3) were monitored by quantitative reverse transcription PCR and Western blot. The pathologic changes of lung tissues were evaluated by Hematoxylin-Eosin staining, immunohistochemistry, and dry and wet method. Meanwhile, the pro-inflammatory factors and proteins were determined by ELISA and Western blot. In contrast, a sepsis model in BEAS-2B was induced with lipopolysaccharide (LPS) to verify the effects of SNHG16/miR-128-3p/HMGB3 on lung epithelial cell viability and apoptosis. RESULTS: As a result, SNHG16 and HMGB3 were up-regulated, while miR-128-3p was down-regulated in sepsis-induced ALI both in vivo and in vitro. Inhibiting SNHG16 reduced the apoptosis and inflammation in the sepsis-induced ALI model. Overexpressing SNHG16 promoted LPS-mediated lung epithelial apoptosis and inhibited cell viability and inflammation, while miR-128-3p had the opposite effects. Mechanistically, SNHG16 targeted miR-128-3p and attenuated its expression, while miR-128-3p targeted the 3' untranslated region of HMGB3. CONCLUSIONS: Overall, down-regulating SNHG16 alleviated the sepsis-mediated ALI by regulating miR-128-3p/HMGB3.

lncRNA SNHG16 Mediates Cell Proliferation and Apoptosis in Cholangiocarcinoma by Directly Targeting miR-146a-5p/GATA6 Axis.

Cholangiocarcinoma (CCA) is a malignant tumour with high recurrence and mortality rates and poor prognosis. However, the pathogenic mechanism remains unclear. In the present study, we aimed to investigate the roles and regulatory mechanism of SNHG16 in the occurrence and development of CCA. Gene Expression Profiling Interactive Analysis (GEPIA) was used to predict the expressions of SNHG16 and GATA6 in CCA samples from TCGA database. The levels of SNHG16, miR-146a-5p and GATA6 were evaluated using qRT-PCR. CCK-8 and flow cytometry assays were conducted to evaluate cell proliferation and apoptosis, respectively. Western blotting was applied to analyse the protein levels of GATA6 and apoptosis-related proteins. SNHG16 was significantly elevated in CCA tissues from TCGA database and CCA cell lines. Moreover, downregulation of SNHG16 restricted cell proliferation and increased apoptotic rate of RBE and HuCCT1 cells. miR-146a-5p, a downstream target of SNHG16, was shown to be an intermediate mediator of GATA6 expression regulated by SNHG16. In addition, either the miR-146a-5p inhibitor or overexpression of GATA6 obviously impaired the regulatory effects of SNHG16 downregulation in RBE and HuCCT1 cells. These data demonstrated that SNHG16 promoted cell proliferation and repressed apoptosis by regulating the miR-146a-5p/GATA6 axis, which provides some helpful insights for the diagnosis and treatment of CCA.

lncRNA SNHG16 promotes glioma tumorigenicity through miR-373/EGFR axis by activating PI3K/AKT pathway.

Glioma is one of the most common and aggressive malignant primary brain tumor with invariably poor 5-year survival rates. Because of the high recurrence rate and mortality rate, effective therapies for glioma are still weak. Recently, several studies has been proved that long non-coding RNAs (lncRNAs) have been identified to play regulatory mediators in the tumorigenesis of glioma. Nevertheless, the role of lncRNAs and their downstream transcripts are still elusive in the progression of glioma. Small nucleolar RNA host gene 16 (SNHG16), a newly identified lncRNA, has been verified to be up-regulated in human malignant carcinomas. In the present study, we confirmed that lncRNA SNHG16 was highly expressed in glioma and may exert oncogenic function as a competing endogenous RNA (ceRNA) to regulate EGFR by sponging of miR-373-3p through activating PI3K/AKT pathway, which providing a new insight of the regulatory network of lncRNA SNHG16 in the development of glioma.

The lncRNA SNHG16 affects prognosis in hepatocellular carcinoma by regulating p62 expression.

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.