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.

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.

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.

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.

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.

Knockdown of lncRNA SNHG16 suppresses multiple myeloma cell proliferation by sponging miR-342-3p.

BACKGROUND: Aberrant expression of long non-coding RNAs (lncRNAs) is closely associated with development and prognosis of human cancers. LncRNA SNHG16 is reportedly involved in human cancer; however, its roles in multiple myeloma (MM) remain unclear. METHODS: In this study, we investigated the function and molecular mechanisms of SNHG16 in MM. MM cells were transfected with si-SNHG16 or si-NC. SNHG16 expression levels was measured by qRT-PCR. Cell proliferation was monitored using the MTS. Flow cytometry assay was performed to measure the cell cycle and apoptosis. Luciferase reporter assay were performed to confirm the sponged miRNAs of SNHG16. RESULTS: SNHG16 expression was up-regulated in MM tissues. SNHG16 knockdown suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted the apoptosis of MM cells. Moreover, SNHG16 knockdown promoted cleaved-Caspase-3, cleaved-Caspase-9, Foxa3a, and Bax expression, while markedly inhibiting CCND1, Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. miR-342-3p was a direct target of SNHG16. SNHG16 knockdown significantly increased miR-342-3p expression in MM cells. Overexpression miR-342-3p markedly suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted apoptosis of MM cells. Overexpression of miR-342-3p markedly promoted cleaved-Caspase-3/-9, Foxa3a, and Bax expression, and inhibited CCND1, Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. Additionally, repression of miR-342-3p could rescue the effect of SNHG16 knockdown on MM cell proliferation, cycle arrest, apoptosis, and related protein expression. CONCLUSION: Knockdown of lncRNA SNHG16 suppresses MM cell proliferation by sponging miR-342-3p, implicating SNHG16 as a novel therapeutic target for MM.

Long non-coding RNA SNHG16 promotes proliferation and inhibits apoptosis of diffuse large B-cell lymphoma cells by targeting miR-497-5p/PIM1 axis.

The aberrant expression and dysfunction of long non-coding RNAs (lncRNAs) have been identified as critical factors governing the initiation and progression of different human cancers, including diffuse large B-cell lymphoma (DLBCL). LncRNA small nucleolar RNA host gene 16 (SNHG16) has been recognized as a tumour-promoting factor in various types of cancer. However, the biological role of SNHG16 and its underlying mechanism are still unknown in DLBCL. Here we disclosed that SNHG16 was overexpressed in DLBCL tissues and the derived cell lines. SNHG16 knockdown significantly suppressed cell proliferation and cell cycle progression, and it induced apoptosis of DLBCL cells in vitro. Furthermore, silencing of SNHG16 markedly repressed in vivo growth of OCI-LY7 cells. Mechanistically, SNHG16 directly interacted with miR-497-5p by acting as a competing endogenous RNA (ceRNA) and inversely regulated the abundance of miR-497-5p in DLBCL cells. Moreover, the proto-oncogene proviral integration site for Moloney murine leukaemia virus 1 (PIM1) was identified as a novel direct target of miR-497-5p. SNHG16 overexpression rescued miR-497-5p-induced down-regulation of PIM1 in DLBCL cells. Importantly, restoration of PIM1 expression reversed SNHG16 knockdown-induced inhibition of proliferation, G0/G1 phase arrest and apoptosis of OCI-LY7 cells. Our study suggests that the SNHG16/miR-497-5p/PIM1 axis may provide promising therapeutic targets for DLBCL progression.

LncRNA SNHG16 induces the SREBP2 to promote lipogenesis and enhance the progression of pancreatic cancer.

Aim: Blocking lipogenesis could significantly inhibit the progression of pancreatic cancer. Exploring the regulatory mechanisms of lipogenesis by lncRNA SNHG16 might be of great significance to control the development of pancreatic cancer. Methods: The proliferation, migration, invasion and lipogenesis were determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, transwell and Oil Red O staining assays, respectively. The interactions among lncRNA SNHG16, miR-195 and SREBP2 were analyzed by dual luciferase reporter assays. Results: Both the knock down of lncRNA SNHG16 and SREBP2 and overexpression of miR-195 suppressed the proliferation, migration, invasion and lipogenesis in pancreatic cancer cells. LncRNA SNHG16 directly sponged miR-195 to modulate the lipogenesis via regulating the expression of SREBP2. Conclusion: LncRNA SNHG16 accelerated the development of pancreatic cancer and promoted lipogenesis via directly regulating miR-195/SREBP2 axis.

Hypoxia Induces Tumor-Derived Exosome SNHG16 to Mediate Nasopharyngeal Carcinoma Progression through the miR-23b-5p/MCM6 Pathway.

This study aims to investigate the mechanism of tumor-derived exosomal (EVs) SNHG16 in promoting the progression of nasopharyngeal carcinoma (NPC). QRT-PCR was used to detect the expression of SNHG16, miR-23b-5p and MCM6 in NPC. MTT, flow cytometry and transwell were used to detect the effects of them on the proliferation, cycle, apoptosis and invasion ability of NPC. Transmission electron microscopy, Western blotting and BCA were used to verify the regulation of exosome secretion under different oxygen environments. Our results showed that hypoxia induces tumor-derived exosome SNHG16 to mediate NPC progression through the miR-23b-5p/MCM6 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.

Mechanism of lncRNA SNHG16 on kidney clear cell carcinoma cells by targeting miR-506-3p/ETS1/RAS/ERK molecular axis.

Objective: This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. Methods: Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. Results: SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P < 0.05). After SNHG16 silence, KIRC cells showed decreased proliferation, invasion and migration capabilities and increased apoptosis rate; correspondingly, increase in SNHG16 expression achieved opposite results (P < 0.05). Finally, in the rescue experiment, the effects of elevated SNHG16 on KIRC cells were reversed by simultaneous increase in miR-506-3p, and the effects of miR-506-3p were reversed by ETS1. Activation of the RAS/ERK pathway had the same effect as increase in ETS1, which further worsened the malignancy of KIRC. After miR-506-3p increase and ETS1 silence, the RAS/ERK signaling pathway was inhibited (P < 0.05). At last, the rescue experiment (co-transfection) confirmed that the effect of SNHG16 on KIRC cells is achieved via the miR-506-3p/ETS1/RAS/ERK molecular axis. Conclusion: SNHG16 regulates the biological behavior of KIRC cells by targeting the miR-506-3p/ETS1/RAS/ERK molecular axis.

Knockdown of lncRNA SNHG16 attenuates myocardial ischemia­reoxygenation injury via targeting miR­183/FOXO1 axis.

Accumulating evidence shows that long non-coding RNAs (lncRNAs) are widely involved in cellular processes of myocardial ischemia/reperfusion (I/R). The present study investigated the functions of lncRNA SNHG16 in myocardial I/R and the mechanism mediated by SNHG16. The myocardial I/R rat and cell model and hypoxia/reoxygenation injury (H/R) models of H9C2 cardiomyocytes were established to detect the expression of SNHG16. Cell Counting Kit-8, flow cytometric and western blot assays were conducted to detect cell viability, apoptosis and protein expression. Myocardial cell apoptosis was assessed by TUNEL staining. Dual-luciferase gene reporter was applied to determine the interaction between the molecules. The expressions of SNHG16 were upregulated in myocardial I/R injury models. Inhibition of SNHG16 relieved myocardial I/R injury in vivo and in vitro silencing of SNHG16 alleviated H/R induced cardiomyocyte apoptosis. To explore the regulatory mechanism, it was discovered that SNHG16 directly interacted with miR-183, while forkhead box O1 (FoxO1) was a target of microRNA (miR)-183. Findings from rescue assays revealed that miR-183 inhibitor and upregulation of FOXO1 can rescue the effect of sh-SNHG16 on H/R-induced cardiomyocyte apoptosis. The results indicated that the lncRNA SNHG16/miR-183/FOXO1 axis exacerbated myocardial cell apoptosis in myocardial I/R injury, suggesting SNHG16 as a potential therapeutic target for myocardial I/R injury.

LncRNA SNHG16 regulates RAS and NF-κB pathway-mediated NLRP3 inflammasome activation to aggravate diabetes nephropathy through stabilizing TLR4.

AIMS: LncRNA SNHG16 and Toll-like receptor-4 (TLR4) participate in diabetes nephropathy. This study investigated whether SNHG16 regulates diabetic renal injury (DRI) via TLR4 and its related mechanism. METHODS: Diabetic mice and high glucose (HG)-induced HRMCs were used to examine the expressions of SNHG16 and TLR4. The SNHG16 expression, cytokines, reactive oxygen species, MDA, SOD, GSH, and fibrosis-related proteins were evaluated in HG-induced HRMCs transfected with sh-NC or sh-SHNG16. RNA immunoprecipitation and RNA pull-down determined the interaction between SNHG16 and EIF4A3 or TLR4 and EIF4A3. We used HG-treated HRMCs or diabetic mice to investigate the roles of TLR4 or SNHG16 in renal injuries. RESULTS: Both SNHG16 and TLR4 were upregulated in diabetic conditions. HG increased serum Scr and BUN, led to significant fibrosis, increased inflammation- and renal fibrosis-related proteins in mice, and increased ROS, MDA, and decreased SOD and GSH in HRMCs. SNHG16 silencing diminished HG-upregulated SNHG16, decreased HG-increased cytokines secretion, ROS, MDA, and fibrosis but increased SOD and GSH. RIP and RNA pull-down confirmed that SNHG16 recruits EIF4A3 to stabilize TLR4 mRNA. TLR4 knockdown alleviated HG-induced renal injuries by suppressing RAS and NF-κB-mediated activation of NLRP3 inflammasomes. SNHG16 knockdown alleviated HG-induced renal injuries in HG-induced HRMCs or diabetic mice. Interestingly, TLR4 overexpression reversed the effects of SNHG16 knockdown. Mechanistically, SNHG16 knockdown alleviated HG-induced renal injuries by suppressing TLR4. CONCLUSION: SNHG16 accelerated HG-induced renal injuries via recruiting EIF4A3 to enhance the stabilization of TLR4 mRNA. The SNGHG16/ELF4A3/TLR4 axis might be a novel target for treating DRI.

Blocking lncRNA-SNHG16 sensitizes gastric cancer cells to 5-Fu through targeting the miR-506-3p-PTBP1-mediated glucose metabolism.

BACKGROUND: Gastric cancer (GC) is a commonly occurring human malignancy. The 5-fluorouracil (5-Fu) is a first-line anti-gastric cancer agent. However, a large number of GC patients developed 5-Fu resistance. Currently, the roles and molecular mechanisms of the lncRNA-SNHG16-modulated 5-Fu resistance in gastric cancer remain elusive. METHODS: Expressions of lncRNA, miRNA, and mRNA were detected by qRT-PCR and Western blot. RNA-RNA interaction was examined by RNA pull-down and luciferase assay. Cell viability and apoptosis rate under 5-Fu treatments were determined by MTT assay and Annexin V assay. The glycolysis rate of GC cells was evaluated by glucose uptake and ECAR. RESULTS: Here, we report that SNHG16 as well as PTBP1, which is an RNA-binding protein, are positively associated with 5-Fu resistance to gastric cancer. SNHG16 and PTBP1 were significantly upregulated in gastric tumors and cell lines. Silencing SNHG16 or PTBP1 effectively sensitized GC cells to 5-Fu. Furthermore, glucose metabolism was remarkedly elevated in 5-Fu-resistant GC cells. Under low glucose supply, 5-Fu-resistant cells displayed higher vulnerability than parental GC cells. Bioinformatic analysis and luciferase assay demonstrated that SNHG16 downregulated miR-506-3p by sponging it to form a ceRNA network. We identified PTBP1 as a direct target of miR-506-3p in GC cells. RNA-seq results unveiled that PTBP1 positively regulated expressions of multiple glycolysis enzymes, including GLUT1, HK2, and LDHA. Bioinformatic analysis illustrated the 3'UTRs of glycolysis enzymes contained multiple PTBP1 binding sites, which were further verified by RNA pull-down and RNA immunoprecipitation assays. Consequently, we demonstrated that PTBP1 upregulated the mRNAs of glycolysis enzymes via promoting their mRNA stabilities. Finally, in vivo xenograft experiments validated that blocking the SNHG16-mediated miR-506-3p-PTBP1 axis effectively limited 5-Fu-resistant GC cell originated-xenograft tumor growth under 5-Fu treatments. CONCLUSIONS: Our study demonstrates molecular mechanisms of the SNHG16-mediated 5-Fu resistance of GC cells through modulating the miR-506-3p-PTBP1-glucose metabolism axis, presenting a promising approach for anti-chemoresistance therapy.

Long non-coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2-mediated epigenetic modification.

Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16) might interact with EZH2, indicating a potential pathway to overcome gemcitabine-resistant PC progression. We investigated the role of the SNHG16/EZH2/Smad4 pathway in gemcitabine-resistant PC cells (PANC-1/GR and SW1990/GR). First, we found that SNHG16 was upregulated both in wild-type PC cells and in gemcitabine-resistant PC cells. SNHG16 overexpression reduced gemcitabine cytotoxicity and apoptosis in PC cells. Meanwhile, SNHG16 upregulation caused p-Akt elevation and Smad4 reduction. However, SNHG16 silencing induced the opposite trend. Then, we found that EZH2 was enriched in SNHG16 based on RIP and RNA pulldown. In particular, SNHG16 overexpression promoted the interaction between EZH2 and the Smad4 promoter according to Chromatin immunoprecipitation-quantitative polymerase chain reaction. Finally, both EZH2 inhibition and Smad4 upregulation increased gemcitabine cytotoxicity and apoptosis in PC cells during SNHG16 overexpression. Moreover, both treatments decreased p-Akt and increased Smad4. Collectively, lncRNA SNHG16 decreased Smad4 to induce GR in PC via EZH2-mediated epigenetic modification.

LncRNA SNHG16 accelerates atherosclerosis and promotes ox-LDL-induced VSMC growth via the miRNA-22-3p/HMGB2 axis.

Long non-coding RNAs (LncRNAs) are essential regulators in the occurrence and development of AS. Here we aim to explore the underlying molecular mechanism of LncRNA SNHG16 in regulating ox-LDL-induced VSMC proliferation, migration and invasion. After constructing AS in vivo and in vitro models, the expressions of SNHG16, miR-22-3p, HMBG2, proliferation- and metastasis-related proteins were determined by qRT-PCR and Western blot assays. Detection of serological lipids, H&E and Masson staining analysis were conducted to evaluate the AS injury in mice. The effects of ox-LDL treatment on VSMCs were examined by CCK-8, wound scratch and Transwell Chamber assays. The targeted relationship was measured by luciferase reporter and RIP assays. The results showed that SNHG16 and high-mobility group box 2 (HMGB2) expressions were increased while miRNA-22-3p expression was decreased in AS mice and ox-LDL-stimulated VSMCs. Functionally, sh-SNHG16 restrained ox-LDL-induced VSMC growth and migration. SNHG16 suppressed miRNA-22-3p expression by direct binding. Furthermore, in ox-LDL-treated VSMCs, miRNA-22-3p mimic prevented proliferation, migration, and invasion. Further explorations showed that HMGB2 was a target of miRNA-22-3p, SNHG16 upregulated HMGB2 levels by acting as a competing endogenous RNA (ceRNA) of miRNA-22-3p. More importantly, sh-HMGB2 partially reversed the effects of sh-SNHG16 together with miR-22-2p inhibitor on ox-LDL-induced VSMC proliferation, migration and invasion. Collectively, SNHG16 accelerated atherosclerotic plaque (AP) formation and enhanced ox-LDL-activated VSMCs proliferation and migration by miRNA-22-3p/HMGB2 axis.

LncRNA SNHG16 Facilitates Nasopharyngeal Carcinoma Progression by Acting as ceRNA to Sponge miR-520a-3p and Upregulate MAPK1 Expression.

BACKGROUND: Accumulating evidence shows that lncRNAs are widely involved cellular processes of various tumors. The aim of this study was to explore the potential role and molecular mechanism of lncRNA SNHG16 in nasopharyngeal carcinoma (NPC). METHODS: SNHG16, miR-520a-3p, and MAPK1 levels were measured by RT-qPCR assay. CCK-8, colony formation, transwell, and flow cytometry assays were adopted to analyze the proliferation, migration, invasion, and apoptosis of NPC cell lines (SUNE1 and 5-8F). Murine xenograft model was used to investigate tumor growth and metastasis in vivo. Immunohistochemical staining was employed to evaluate the levels of Bcl-2, cleaved caspase-3, Bax, and Ki-67. Dual-luciferase reporter assays were conducted to analyze the binding ability between miR-520a-3p and SNHG16 or MAPK1. RESULTS: SNHG16 was overexpressed in NPC tissues and cells. High SNHG16 expression indicated a poor prognosis. SNHG16 knockdown could cause significant inhibition on cell proliferation and metastasis, induce cell apoptosis in NPC cells, and repressed tumor growth and metastasis in vivo. Additionally, SNHG16 could directly bind to miR-520a-3p, thus positively regulating MAPK1 expression. Moreover, functional analysis indicated that miR-520a-3p exerted a tumor-suppressing role in NPC progression. Rescue assays demonstrated that MAPK1 upregulation could abrogate the inhibitory effects on NPC cell proliferation and metastasis, as well as the promoting effects on NPC cell apoptosis caused by SNHG16 knockdown. In conclusion, SNHG16 contributed to the proliferation and metastasis of NPC cells by modulating the miR-520a-3p/MAPK1 axis. CONCLUSION: These results suggest that SNHG16 acts as an oncogene in the progression of NPC via modulating the miR-520a-3p/MAPK1 axis.

Extracellular Vesicles Carry lncRNA SNHG16 to Promote Metastasis of Breast Cancer Cells via the miR-892b/PPAPDC1A Axis.

Breast cancer (BC) represents the most commonly diagnosed malignancy among women. Long non-coding RNAs (lncRNAs) can be transferred by extracellular vesicles (EVs) to participate in BC progression. This study demonstrated that SNHG16 expression was significantly increased in BC tissues and cells. Overexpression of SNHG16 promoted the migration, invasion, and epithelial-mesenchymal transition (EMT) of BC cells. SNHG16 was carried by EVs. Bioinformatics analysis predicted that SNHG16 regulated PPAPDC1A expression by sponging miR-892b, which was confirmed by RNA-fluorescence in situ hybridization (FISH), RT-qPCR, dual-luciferase gene reporter assay, and RNA immunoprecipitation (RIP). MDA-MB-157 and HS578T cells were transfected with pcDNA3.1-SNHG16, miR-892b-mimic, or si-PPAPDC1A for functional rescue experiments in vitro, and the cells were treated with MDA-MB-231 cell-derived EVs. The results confirmed that enhanced miR-892b expression partially eliminated the increase of migration, invasion, and EMT of BC cells mediated by SNHG16 or EVs. The lung metastasis model in nude mice was established by injecting HS578T cells via tail vein. The results showed that si-SNHG16 reduced the metastatic nodules and decreased the vimentin expression. In conclusion, EVs derived from BC cells transferred SNHG16 via the miR-892b/PPAPDC1A axis, thus promoting EMT, migration, and invasion of BC.

Silencing of LncRNA SNHG16 Downregulates Cyclin D1 (CCND1) to Abrogate Malignant Phenotypes in Oral Squamous Cell Carcinoma (OSCC) Through Upregulating miR-17-5p.

BACKGROUND: Targeting the long non-coding RNAs (LncRNAs)-microRNAs (miRNAs)-mRNA competing endogenous RNA (ceRNA) networks has been proved as an effective strategy to treat multiple cancers, including oral squamous cell carcinoma (OSCC). Based on this, the present study identified a novel LncRNA SNHG16/miR-17-5p/CCND1 signaling pathway that played an important role in regulating the pathogenesis of OSCC. METHODS: The expression levels of cancer-associated genes were examined by Real-Time qPCR and Western Blot at transcriptional and translated levels, respectively. CCK-8 assay was performed to determine cell proliferation, and cell apoptosis ratio was measured by the Annexin V-FITC/PI double staining assay. Transwell assay was performed to examine cell migration, and dual-luciferase reporter gene system assay was used to validate the ceRNA networks. RESULTS: LncRNA SNHG16 and CCND1 were upregulated, while miR-17-5p was downregulated in OSCC tissues and cell lines, compared to their normal counterparts. Also, miR-17-5p negatively correlated with both LncRNA SNHG16 and CCND1 mRNA, but LncRNA SNHG16 was positively relevant to CCND1 mRNA in OSCC tissues. By performing the gain- and loss-of-function experiments, we noticed that LncRNA SNHG16 overexpression aggravated the malignant phenotypes, such as cell proliferation, viability, migration and epithelial-mesenchymal transition (EMT) in OSCC cells, while LncRNA SNHG16 knock-down had opposite effects. Furthermore, our dual-luciferase reporter gene system evidenced that LncRNA SNHG16 sponged miR-17-5p to upregulate CCND1 in OSCC cells, and the inhibiting effects of LncRNA SNHG16 ablation on OSCC progression were abrogated by both downregulating miR-17-5p and overexpressing CCND1. Finally, the xenograft tumor-bearing mice models were established, and our data validated that LncRNA SNHG16 served as an oncogene to promote tumorigenicity of OSCC cells in vivo. CONCLUSION: Taken together, targeting the LncRNA SNHG16/miR-17-5p/CCND1 axis hindered the development of OSCC, and this study provided potential diagnostic and therapeutic biomarkers for OSCC in clinic.