LncRNA SNHG12 suppresses adipocyte inflammation and insulin resistance by regulating the HDAC9/Nrf2 axis.

Obesity is often associated with low-grade inflammation. The incidence of obesity has increased annually worldwide, which seriously affects human health. A previous study indicated that long noncoding RNA SNHG12 was downregulated in obesity. Nevertheless, the role of SNHG12 in obesity remains to be elucidated. In this study, qRT-PCR, western blot, and ELISA were utilized to examine the gene and protein expression. Flow cytometry was employed to investigate the M2 macrophage markers. RNA pull-down assay and RIP were utilized to confirm the interactions of SNHG12, hnRNPA1, and HDAC9. Eventually, a high-fat diet-fed mouse model was established for in vivo studies. SNHG12 overexpression suppressed adipocyte inflammation and insulin resistance and promoted M2 polarization of macrophages that was caused by TNF-α treatment. SNHG12 interacted with hnRNPA1 to downregulate HDAC9 expression, which activated the Nrf2 signaling pathway. HDAC9 overexpression reversed the effect of SNHG12 overexpression on inflammatory response, insulin resistance, and M2 phenotype polarization. Overexpression of SNHG12 improved high-fat diet-fed mouse tissue inflammation. This study revealed the protective effect of SNHG12 against adipocyte inflammation and insulin resistance. This result further provides a new therapeutic target for preventing inflammation and insulin resistance in obesity.

The SNHG12/microRNA-15b-5p/MYLK axis regulates vascular smooth muscle cell phenotype to affect intracranial aneurysm formation.

OBJECTIVE: This research was dedicated to investigating the impact of the SNHG12/microRNA (miR)-15b-5p/MYLK axis on the modulation of vascular smooth muscle cell (VSMC) phenotype and the formation of intracranial aneurysm (IA). METHODS: SNHG12, miR-15b-5p and MYLK expression in IA tissue samples from IA patients were tested by RT-qPCR and western blot. Human aortic vascular smooth muscle cells (VSMCs) were cultivated with H2O2 to mimic IA-like conditions in vitro, and the cell proliferation and apoptosis were measured by MTT assay and Annexin V/PI staining. IA mouse models were established by induction with systemic hypertension combined with elastase injection. The blood pressure in the tail artery of mice in each group was assessed and the pathological changes in arterial tissues were observed by HE staining and TUNEL staining. The expression of TNF-α and IL-1ß, MCP-1, iNOS, caspase-3, and caspase-9 in the arterial tissues were tested by RT-qPCR and ELISA. The relationship among SNHG12, miR-15b-5p and MYLK was verified by bioinformatics, RIP, RNA pull-down, and luciferase reporter assays. RESULTS: The expression levels of MYLK and SNHG12 were down-regulated and that of miR-15b-5p was up-regulated in IA tissues and H2O2-treated human aortic VSMCs. Overexpressed MYLK or SNHG12 mitigated the decrease in proliferation and increase in apoptosis of VSMCs caused by H2O2 induction, and overexpression of miR-15b-5p exacerbated the decrease in proliferation and increase in apoptosis of VSMCs caused by H2O2 induction. Overexpression of miR-15b-5p reversed the H2O2-treated VSMC phenotypic changes caused by SNHG12 up-regulation, and overexpression of MYLK reversed the H2O2-treated VSMC phenotypic changes caused by up-regulation of miR-15b-5p. Overexpression of SNHG12 reduced blood pressure and ameliorated arterial histopathological damage and VSMC apoptosis in IA mice. The mechanical analysis uncovered that SNHG12 acted as an endogenous RNA that competed with miR-15b-5p, thus modulating the suppression of its endogenous target, MYLK. CONCLUSION: Decreased expression of SNHG12 in IA may contribute to the increasing VSMC apoptosis via increasing miR-15b-5p expression and subsequently decreasing MYLK expression. These findings provide potential new strategies for the clinical treatment of IA.

LncRNA SNHG12 regulated by WTAP aggravated the oxygen-glucose deprivation/reperfusion-induced injury in bEnd.3 cell.

OBJECTIVES: Previous studies have identified abnormal expression of lncRNA SNHG12 in ischemic stroke, but the underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Through database predictions, m6A methylation sites were found on SNHG12, suggesting post-transcriptional modification. To further elucidate the role of SNHG12 and m6A methyltransferase WTAP in oxygen-glucose deprivation/reperfusion (OGD/R)-induced damage in cerebral microvascular endothelial cells, we conducted investigations. Additionally, we examined the impact of m6A methyltransferase WTAP on SNHG12 expression. RESULTS: Overexpressing SNHG12 in bEnd.3 cells was found to inhibit cell proliferation and promote apoptosis, as well as activate the production of reactive oxygen species and inflammatory cytokines (E-selectin, IL-6 and MCP-1), along with angiogenic proteins (VEGFA and FGFb). Conversely, SNHG12 knockdown alleviated OGD/R-induced damage to BEnd.3 cells, resulting in improved cell proliferation, reduced apoptosis, decreased ROS and LDH production, as well as diminished expression of inflammatory cytokines (E-selectin, IL-6 and MCP-1) and angiogenic proteins (VEGFA and FGFb). Furthermore, WTAP was found to positively regulate SNHG12 expression, and WTAP knockdown in bEnd.3 cells under the OGD/R conditions inhibited cell proliferation, promoted apoptosis, and increased ROS and LDH production. CONCLUSION: These findings suggest that WTAP may play a crucial role in SNHG12-mediated OGD/R-induced damage in bEnd.3 cells. More molecular experiments are needed to further analyze its mechanism. Overall, our study helps to enrich our understanding of the dysregulation of SNHG12 in ischemic stroke.

[Effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of prostate cancer cells by regulating E2F5 expression].

OBJECTIVE: To analyze the effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of PCa cells by regulating the expression of E2F5. METHODS: Using real time fluorescence RT-PCR, we detected the expressions of lncRNA SNHG12 and E2F5, constructed the PC3 cells inhibiting the lncRNA SNHG12 expression. After transfection of the PC3 cells, we divided them into an NC, a si-NC, a si-SNHG12, a si-E2F5, a si-SNHG12+OE-si-NC, and a si-SNHG12+OE-E2F5 group, followed by examination of the proliferation, apoptosis, migration and invasiveness of the cells in different groups. RESULTS: The expressions of lncRNA SNHG12 and E2F5 were significantly up-regulated in the PCa tissue compared with those in the adjacent tissue (P < 0.05), remarkably higher in the DU145, LNCaP and PC3 groups than in the RWPE-1 group, the highest in the PC3 group (P < 0.05). The expression of SNHG12 was markedly down-regulated in the si-SNHG12 group (P < 0.05) in comparison with that in the si-NC group, indicating the successful construction of a PC3 cell line interfering with the lncRNA SNHG12 expression. Compared with the si-NC group, the si-SNHG12 group showed significant decreases in the values of CyclinD1, MMP-9 and OD and the numbers of migrating and invading cells, and an increase in apoptotic cells (P < 0.05), while the si-E2F5 group exhibited a remarkably down-regulated expression of E2F5 (P < 0.05), reduced values of CyclinD1, MMP-9 and OD, decreased numbers of migrating and invading cells and an increased number of apoptotic cells (P < 0.05). The dual luciferase report test showed that E2F5 reduced the luciferase activity of SNHG12 (P < 0.05 and had an insignificant impact on the luciferase activity of MUT-SNHG12 (P > 0.05). Inhibiting the expression of lncRNA SNHG12 resulted in significant decreases in the expression of E2F5, values of CyclinD1, MMP-9 and OD and numbers of migrating and invading cells, but an increase in apoptotic cells (P < 0.05). The E2F5 expression, the CyclinD1, MMP-9 and OD values and the numbers of migrating and invading cells were markedly increased while the number of apoptotic cells decreased in the si-SNHG12+OE-E2F5 group compared with those in the si-SNHG12+OE-si-NC group (P < 0.05). CONCLUSION: Interfering with the expression of lncRNA SNHG12 can regulate that of E2F5, inhibit the proliferation, migration and invasiveness of PCa cells and promote their apoptosis.

Octreotide ameliorates hepatic ischemia-reperfusion injury through SNHG12/TAF15-mediated Sirt1 stabilization and YAP1 transcription.

BACKGROUND: Hepatic ischemia-reperfusion (HIR) injury is a pathological condition initiated by interrupted hepatic blood supply and exaggerated after reperfusion, which is one of the most lethal risks in liver transplantation and other liver surgeries. We aimed to investigate the protective mechanism of octreotide (Oct) against HIR injury. METHODS: The function of Oct was evaluated in the in vivo mouse model of HIR injury. Histological examinations were performed to assess the pathological changes. Serum parameters including ALT and AST were measured to evaluate the liver damage. qRT-PCR and western blot analysis were employed to determine the levels of long non-coding RNA SNHG12 (SNHG12) and autophagy or apoptosis-related proteins. RNA pull-down and RIP assays were used to verify the interaction between SNHG12 and TAF15. The transcriptional regulation of TAF15 in YAP1 was validated by ChIP and luciferase reporter assays. RESULTS: In the in vivo HIR injury model, Oct efficiently alleviated HIR-caused hepatic damage by suppressing apoptosis and activating autophagy. However, silencing of SNHG12 abrogated the protective effects of Oct via inactivating autophagy. Further mechanism investigation revealed that SNHG12 promoted the stabilization of Sirt1 and increased YAP1 transcriptional activity via interacting with TAF15. Up-regulation of Sirt1 and YAP1 was essential for maintaining the protective effect of Oct against HIR injury through increasing autophagic flux and suppressing apoptosis. CONCLUSIONS: Oct-induced up-regulation of SNHG12 attenuated HIR injury via promoting Sirt1 stabilization and YAP1 transcription to activate autophagy and repress apoptosis.

KMT2B promotes the growth of renal cell carcinoma via upregulation of SNHG12 expression and promotion of CEP55 transcription.

BACKGROUND: This study aims to clarify the mechanistic action of long non-coding RNA (lncRNA) SNHG12 in the development of renal cell carcinoma (RCC), which may be associated with promoter methylation modification by KMT2B and the regulation of the E2F1/CEP55 axis. METHODS: TCGA and GEO databases were used to predict the involvement of SNHG12 in RCC. Knockdown of SNHG12/E2F1/CEP55 was performed. Next, SNHG12 expression and other mRNAs were quantified by RT-qPCR. Subsequently, CCK-8 was used to detect cell proliferation. Wound healing assay and Transwell assay were used to detect cell migration and invasion, respectively. The in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs) was explored by matrigel-based capillary-like tube formation assay. ChIP assay was used to detect H3K4me3 in SNHG12 promoter region. The binding of E2F1 to CEP55 promoter region was analyzed with ChIP and dual luciferase reporter assays. RIP assay was used to detect the binding of SNHG12 to E2F1. Finally, the effect of SNHG12 on the tumor formation and angiogenesis of RCC was assessed in nude mouse xenograft model. RESULTS: SNHG12 was highly expressed in RCC tissues and cells, and it was related to the poor prognosis of RCC patients. SNHG12 knockdown significantly inhibited RCC cell proliferation, migration, and invasion and HUVEC angiogenesis. KMT2B up-regulated SNHG12 expression through modifying H3K4me3 in its promoter region. In addition, SNHG12 promoted CEP55 expression by recruiting the transcription factor E2F1. Knockdown of SNHG12 blocked E2F1 recruitment and down-regulated the expression of CEP55, thereby inhibiting tumor formation and angiogenesis in nude mice. CONCLUSION: The evidence provided by our study highlighted the involvement of KMT2B in up-regulation of lncRNA as well as the transcription of CEP55, resulting in the promotion of angiogenesis and growth of RCC.

Molecular mechanism of lncRNA SNHG12 in immune escape of non-small cell lung cancer through the HuR/PD-L1/USP8 axis.

BACKGROUND: The pivotal role of long noncoding RNAs (lncRNAs) in cancer immune responses has been well established. This study was conducted with the aim of exploring the molecular mechanism of lncRNA small nucleolar RNA host gene 12 (SNHG12) in immune escape of non-small cell lung cancer (NSCLC). METHODS: Expression of lncRNA SNHG12, programmed cell death receptor ligand 1 (PD-L1), ubiquitin-specific protease 8 (USP8), and human antigen R (HuR) in NSCLC tissues and cells was measured, and their binding relationship was determined. NSCLC cell proliferation and apoptosis were assessed. Peripheral blood mononuclear cells (PBMCs) were co-cultured with NSCLC cells. The ratio of CD8+ T cells, PBMC proliferation, and inflammatory factors were determined. lncRNA SNHG12 localization was assessed via subcellular fractionation assay. The half-life period of mRNA was determined using actinomycin D. Xenograft tumor models were established to confirm the role of lncRNA SNHG12 in vivo. RESULTS: LncRNA SNHG12 was found to be prominently expressed in NSCLC tissues and cells, which was associated with a poor prognosis. Silencing lncRNA SNHG12 resulted in the reduction in proliferation and the promotion of apoptosis of NSCLC cells, while simultaneously increasing PBMC proliferation and the ratio of CD8+ T cells. Mechanically, the binding of lncRNA SNHG12 to HuR improved mRNA stability and expression of PD-L1 and USP8, and USP8-mediated deubiquitination stabilized the protein level of PD-L1. Overexpression of USP8 or PD-L1 weakened the inhibition of silencing lncRNA SNHG12 on the immune escape of NSCLC. Silencing lncRNA SNHG12 restricted tumor growth and upregulated the ratio of CD8+ T cells by decreasing USP8 and PD-L1. CONCLUSION: LncRNA SNHG12 facilitated the immune escape of NSCLC by binding to HuR and increasing PD-L1 and USP8 levels.

miR-140-3p is involved in the occurrence and metastasis of gastric cancer by regulating the stability of FAM83B.

BACKGROUND: Gastric cancer (GC) is a malignant tumor and microRNAs (miRNAs) are closely connected to GC development. The purpose of this study is to investigate the effect of miR-140-3p on the occurrence and metastasis of GC. METHODS: We detected miR-140-3p expression in GC cells and tissues. The correlation between miR-140-3p and prognosis and clinicopathological features in GC was analyzed. The role of miR-140-3p in GC cell migration, invasion, and proliferation was analyzed. The model of tumor transplantation and metastasis in nude mice was established, and the effect of miR-140-3p on the development and metastasis of GC was assessed. The relation between miR-140-3p and SNHG12 and the relations among HuR, SNHG12, and FAM83B were analyzed. RESULTS: miR-140-3p was poorly expressed in GC. GC patients with low miR-140-3p expression had a poor prognosis and unfavorable clinicopathologic features. Overexpression of miR-140-3p inhibited GC cell migration, invasion, and proliferation, and inhibited the development and metastasis of GC. miR-140-3p directly bound to SNHG12 in GC tissues and downregulated SNHG12 expression. SNHG12 overexpression induced HuR nuclear transportation. HuR can bind to FAM83B and up-regulate the mRNA level of FAM83B. Overexpression of SNHG12 or FAM83B reduced the inhibition of overexpression of miR-140-3p on GC. CONCLUSION: miR-140-3p directly bound to SNHG12 in GC and down-regulated the expression of SNHG12, reduced the binding of SNHG12 and HuR, thus inhibiting the nuclear transportation of HuR and the binding of HuR and FAM83B, and reducing the transcription of FAM83B, and finally inhibiting the growth and metastasis of GC.

LncRNA SNHG12 downregulates RAGE to attenuate hypoxia-reoxygenation-induced apoptosis in H9c2 cells.

Ischemia-reperfusion (I/R) injury causes cardiac dysfunction through several mechanisms including the irregular expression of some long noncoding RNA. However, the role of SNHG12 in myocardial I/R injury remains unclear. Here, we found the increase of the SNHG12 level in hypoxia-reoxygenation (H/R)-injured-H9c2 cells. SNHG12 silencing enhanced the apoptosis of H/R-injured H9c2 cells, while SNHG12 overexpression relieved the cardiomyocyte apoptosis induced by H/R stimulation. Additionally, the suppression of SNHG12 significantly boosted the H/R-induced expression and the production of TNF-α, IL-6, and IL-1ß, as well as the activation of NF-κB, which were fully reversed after overexpression of SNHG12. Mechanistically, SNHG12 adversely regulated the production of receptor for advanced glycation end products (RAGE) in H/R-stimulated H9c2 cells. Antibody blocking of RAGE alleviated the apoptosis of H/R-injured H9c2 cells. Collectively, we have determined a valuable mechanism by which the high level of SNHG12 contributes to H9c2 cells against H/R injury through the reduction of RAGE expression.

Long noncoding RNA SNHG12 indicates the prognosis of prostate cancer and accelerates tumorigenesis via sponging miR-133b.

Prostate cancer (PCa) is the second leading cause of death among American men. Increasing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis of PCa. In this study, we explored the biological functions of small nucleolar RNA host gene 12 (SNHG12) and investigated the interaction between miR-133b and SNHG12 in the progression of PCa. Data was downloaded from The Cancer Genome Atlas and Human Cancer Metastasis Database, and clinicopathological characteristics were analyzed with relapse-free survival rate. We detected SNHG12 expression level in PCa cells and tissues, and then analyzed its clinical significance, which revealed that SNHG12 has the potent to predict prognosis of PCa. Bioinformatic analysis revealed that SNHG12 was closely related to the progression of PCa and could target candidate microRNA (miR-133b). After transfecting SNHG12 silencing plasmid and miR-133b mimic/sponge, biological function assays were conducted and results illustrated that SNHG12 associated with miR-133b exerted biological effects on cancer cell growth, migration, and invasion. Direct interactions between miR-133b and SNHG12 have been found and SNHG12 acts as an oncogene to promote tumorigenesis of PCa by sponging tumor suppressor gene miR-133b.

Long noncoding RNA SNHG12 modulated by human papillomavirus 16 E6/E7 promotes cervical cancer progression via ERK/Slug pathway.

Recently, long noncoding RNA SNHG12 has been reported to be dysregulated in various types of cancer. This study investigated its biological function and the underlying molecular mechanism in cervical squamous cell carcinoma (CSCC). We found that SNHG12 was significantly overexpressed in CSCC tissues. Further evidence showed that human papillomavirus (HPV) type 16 E6 and E7 might regulate the expression level of SNHG12 by modulating transcription factor c-Myc. Functional experiments suggested that SNHG12 knockdown dramatically repressed CSCC cells proliferation, migration, and invasion while induced apoptosis in vitro as well as suppressed tumor growth in vivo. In addition, SNHG12 could facilitate epithelial-mesenchymal transition through ERK/Slug/E-cadherin pathway at least in part. Our findings highlight SNHG12 functions as an oncogenic long noncoding RNA in malignant phenotype and tumorigenesis of CSCC, which implicate it may be a potential target for CSCC treatment.

DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma.

BACKGROUND: Accumulating evidence shows that long noncoding RNAs (lncRNAs) are important regulator molecules involved in diverse biological processes. Acquired drug resistance is a major challenge in the clinical treatment of glioblastoma (GBM), and lncRNAs have been shown to play a role in chemotherapy resistance. However, the underlying mechanisms by which lncRNA mediates TMZ resistance in GBM remain poorly characterized. METHODS: Quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization assays were used to detect small nucleolar RNA host gene 12 (SNHG12) levels in TMZ-sensitive and TMZ-resistant GBM cells and tissues. The effects of SNHG12 on TMZ resistance were investigated through in vitro assays (western blots, colony formation assays, flow cytometry assays, and TUNEL assays). The mechanism mediating the high expression of SNHG12 in TMZ-resistant cells and its relationships with miR-129-5p, mitogen-activated protein kinase 1 (MAPK1), and E2F transcription factor 7 (E2F7) were determined by bioinformatic analysis, bisulfite amplicon sequencing, methylation-specific PCR, dual luciferase reporter assays, chromatin immunoprecipitation assays, RNA immunoprecipitation assays, immunofluorescence, qRT-PCR, and western blot. For in vivo experiments, an intracranial xenograft tumor mouse model was used to investigate SNHG12 function. RESULTS: SNHG12 was upregulated in TMZ-resistant cells and tissues. Overexpression of SNHG12 led to the development of acquired TMZ resistance, while knockdown of SNHG12 restored TMZ sensitivity. An abnormally low level of DNA methylation was detected within the promoter region of SNHG12, and loss of DNA methylation made this region more accessible to the Sp1 transcription factor (SP1); this indicated that methylation and SP1 work together to regulate SNHG12 expression. In the cytoplasm, SNHG12 served as a sponge for miR-129-5p, leading to upregulation of MAPK1 and E2F7 and endowing the GBM cells with TMZ resistance. Disinhibition of MAPK1 regulated TMZ-induced cell apoptosis and the G1/S cell cycle transition by activating the MAPK/ERK pathway, while E2F7 dysregulation was primarily associated with G1/S cell cycle transition. Clinically, SNHG12 overexpression was associated with poor survival of GBM patients undergoing TMZ treatment. CONCLUSION: Our results suggest that SNHG12 could serve as a promising therapeutic target to surmount TMZ resistance, thereby improving the clinical efficacy of TMZ chemotherapy.

LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway.

BACKGROUND: Radiation resistance is a major obstacle to the prognosis of cervical cancer (CC) patients. Many studies have confirmed that long non-coding RNAs (lncRNAs) are involved in the regulation of radiosensitivity of cancers. However, whether small nucleolar RNA host gene 12 (SNHG12) regulates the radiosensitivity of CC remains unknown. METHODS: Quantitative real-time polymerase chain reaction was used to measure the expression levels of SNHG12 and microRNA-148a (miR-148a). The radiosensitivity of cells was evaluated by clonogenic assay. Flow cytometry and caspase-3 activity assay were performed to assess the apoptosis ability and cell cycle distribution of cells. Besides, dual-luciferase reporter and RNA immunoprecipitation assay were used to verify the interaction between miR-148a and SNHG12 or cyclin-dependent kinase 1 (CDK1). Also, the protein levels of CDK1, CCND1 and γ-H2AX were detected by western blot analysis. Furthermore, in vivo experiments were conducted to verify the effect of SNHG12 on CC tumor growth. Ki-67 and TUNEL staining were employed to evaluate the proliferation and apoptosis rates in vivo. The hematoxylin and eosin (HE) staining were employed to evaluate the tumor cell morphology. RESULTS: SNHG12 was upregulated in CC tissues and cells, and its knockdown improved the radiosensitivity by promoting the radiation-induced apoptosis and cell cycle arrest of CC cells. Also, miR-148a could be sponged by SNHG12 and could target CDK1. MiR-148a inhibitor or CDK1 overexpression could invert the promotion effect of silenced-SNHG12 on CC radiosensitivity. Meanwhile, SNHG12 interference reduced the tumor growth of CC, increased miR-148a expression, and inhibited CDK1 level in vivo. CONCLUSION: LncRNA SNHG12 promoted CDK1 expression to regulate the sensitivity of CC cells to radiation through sponging miR-148a, indicating that SNHG12 could be used as a potential biomarker to treat the radiotherapy resistance of CC patients.

Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer.

BACKGROUND: KLF5 is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers. KLF5 functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated by KLF5 in CRC are currently unknown. METHODS: In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets of KLF5 in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors of KLF5 were then searched for through bioinformatics analysis. We also constructed a regulatory network for KLF5 and annotated its functions. Finally, one of the KLF5 lncRNA targets, SNHG12, was selected to further explore its expression pattern and functions in CRC. RESULTS: We were able to identify 19 lncRNA targets of KLF5 and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factors AR and HSF1 as the regulatory co-factors of KLF5 through bioinformatics analysis. Then, through the analysis of the regulatory network, we found that KLF5 may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, the SNHG12 up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates that SNHG12 may play a critical part in CRC tumorigenesis and progression. Additionally, expression of SNHG12 was found to be down-regulated in CRC cell lines when KLF5 expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels of SNHG12 and KLF5, further alluding to their regulatory relationship. CONCLUSIONS: In conclusion, the network analysis of KLF5 targets indicates that SNHG12 may be a significant lncRNA in CRC.

SNHG12/miR-326/E2F1 feedback loop facilitates the progression of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a kind of common malignant tumor worldwide. An increasing number of researches have validated that long non-coding RNAs (lncRNAs) are closely associated with the occurrence and development of multiple diseases, including cancers. However, the role of lncRNA SNHG12 in OSCC was largely unknown. In present study, qRT-PCR manifested the upregulation of SNHG12 expression in OSCC tissues and cells. Suppression of SNHG12 inhibited cell proliferation, migration, invasion, and EMT process in OSCC. Additionally, SNHG12 depletion also attenuated OSCC tumor growth in vivo. Thereafter, E2F1 was found to be a transcription factor of SNHG12 to stimulate its expression. More interestingly, SNHG12 deficiency reduced E2F1 expression in turn. MiR-326 was found to be shared between SNHG12 and E2F1. Besides, SNHG12 augmented E2F1 in OSCC through miR-326 sequestration. Finally, rescue assays demonstrated that overexpressed E2F1 restored the inhibitory effect resulted from SNHG12 silence, indicating that SNHG12 promoted the progression of OSCC by E2F1-dependent way. This research unveiled that SNHG12/miR-326/E2F1 feedback loop facilitated OSCC progression, which shed new light on therapeutic methods in OSCC.

Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR-125b/STAT3 axis.

Increasing evidence showed that long noncoding RNAs (lncRNAs) played an important role in the occurrence and development of tumors. To date, lncRNA small nucleolar RNA host gene 12 (SNHG12) has revealed an oncogenic role in various tumors. However, the role of SNHG12 in cervical cancer is still unclear. Therefore, we focused on the biological function and molecular mechanism of SNHG12 in the tumorigenesis of cervical cancer. In this study, the expression of miR-125b was observably downregulated in cervical cancer cells. Meanwhile, the expression of SNHG12 was obviously upregulated in cervical cancer cell lines (HeLa, SiHa, Caski, C4-1, and C33A) compared with the immortalized cervical epithelial cells. The further assay showed that miR-125b was a target of SNHG12 in cervical cancer. Moreover, a negative relationship between miR-125b and SNHG12 was found in cervical cancer. In addition, SNHG12 inhibition restrained the proliferation, migration, and invasion of cervical cancer cells. Meanwhile, miR-125b mimics repressed the expression of signal transducer and activator of transcription 3 (STAT3). The further assay showed that STAT3 was a target of miR-125b in cervical cancer. In addition, sh-STAT3 repressed the migration and invasion of cervical cancer cells. Furthermore, it showed that miR-125b inhibitors reversed STAT3 expression restrained by the reduction of SNHG12 expression. In general, SNHG12 modulated STAT3 by sponging miR-125b in cervical cancer and played an important role in the development of cervical cancer.

c-Myc mediated upregulation of long noncoding RNA SNHG12 regulates proliferation and drug sensitivity in natural killer/T-cell lymphoma.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor outcomes. The treatment of NKTCL requires intensive chemotherapy. Long noncoding RNAs (lncRNAs) have been implicated in many cancers, including NKTCL. The elucidation of the multidrug resistance (MDR) may greatly contribute to explore novel therapeutic strategies. Herein, we explored the roles and potential regulatory mechanism of lncRNAs small nucleolar RNA host gene 12 (SNHG12) in MDR of NKTCL. We found that SNHG12 was upregulated in NKTCL tissue sections, and its high expression was positively correlated with clinical grade of malignancy of NKTCL. c-Myc and SNHG12 expression was upregulated in NKTCL cell lines. c-Myc- and SNHG12 overexpression promoted proliferation and inhibited sensitivity to cisplatin (CDDP) in NK/T-cell lymphoma cell line YTS cells, and c-Myc and SNHG12-downregulation inhibited proliferation and enhanced sensitivity to CDDP in SNK-6 cells. Moreover, c-Myc- and SNHG12 overexpression increased Ki67 and P-gp expression in YTS cells, whereas c-Myc and SNHG12-downregulation reduced the Ki67 and P-gp expression in SNK-6 cells. Correlational analyses revealed that c-Myc expression was positively correlated with SNHG12 expression in NKTCL tissues. Mechanism research showed that SNHG12 was a direct transcriptional target of c-Myc and c-Myc promoted SNHG12 expression in NKTCL cell lines. Further research showed that SNHG12 overexpression reversed the effects of c-Myc downregulation on proliferation and sensitivity to CDDP in NKTCL cell lines. Taken together, our findings first report that c-Myc mediated upregulation of SNHG12 promotes proliferation and inhibits drug sensitivity in NKTCL, which provides new insights into the therapeutic target for NKTCL.

Long noncoding RNA SNHG12 promotes cell proliferation and activates Wnt/ß-catenin signaling in prostate cancer through sponging microRNA-195.

Long noncoding RNAs (lncRNAs) serve critical roles in multiple human malignant tumors, including prostate cancer (PCa). Currently, the biological role of oncogenic lncRNA SNHG12 in PCa remains largely unclear. In the present study, we found that SNHG12 was highly expressed in human PCa tissues and cell lines. In addition, gain-of-function and loss-of-function studies showed that overexpression of SNHG12 promoted, while downregulation suppressed the proliferation, invasion, and migration of PCa cells in vitro. Knockdown of SNHG12 also repressed PCa xenograft tumor growth in vivo. Further in-depth mechanistic studies showed that SNHG12 might serve as a competing endogenous RNA for miR-195 in PCa cells, and miR-195 expression level was negatively associated with the expression of SNHG12 in PCa tissues. Finally, we found that the activity of Wnt/ß-catenin signaling is enhanced by SNHG12 overexpression and rescued by co-transfection with miR-195 mimics in PCa cells. Collectively, the present study indicated the oncogenic function of SNHG12 in PCa and our findings might provide a new target in the treatment of PCa.

LncRNA SNHG12 as a potent autophagy inducer exerts neuroprotective effects against cerebral ischemia/reperfusion injury.

Long-non-coding RNA small nucleolar RNA host gene 12(SNHG12) was reported to be highly up-regulated in brain microvascular endothelium after cerebral ischemia. Autophagy has been shown to have protective effects against cerebral ischemic insults. However, molecular mechanisms of SNHG12 in regulating autophagy during cerebral ischemia/reperfusion (I/R) injury remain unclear. Here, we established middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice and adopted oxygen-glucose deprivation and reperfusion (OGD/R) SH-SY5Y cell model to mimic cerebral I/R injury in vitro. Triphenyltetrazolium chloride (TTC) staining was used to measure infarct size. Bederson and Longa score systems were used to evaluate neurological behavioral and defects, respectively. CCK-8, EdU staining, flow cytometry and Hoechst 33258 staining were performed to determine the biological function of SNHG12 on SH-SY5Y cell under OGD/R condition. The autophagy levels were determined by Western blotting and LC3B immunofluorescence. We found the expression of SNHG12 was up-regulated by cerebral I/R in mice andSH-SY5Y cell model after OGD/R. Up-regulated SNHG12 alleviated OGD/R-induced SH-SY5Y cell injury and induced autophagy activation, as indicated by an increased ratio of LC3 II/I and Beclin-1, decreased p62. On the contrary, down-regulation of SNHG12 exacerbated SH-SY5Y cell injury after OGD/R and inhibited autophagy. Furthermore, autophagy activator rapamycin or inhibitor 3-MA partially reversed the down-regulation or up-regulation of SNHG12 effect in OGD/R-inducedSH-SY5Y cell injury, respectively. Taken together, these findings suggest that SNHG12 as an autophagy inducer alleviates cerebral I/R injury, which might be a new therapeutic target of ischemic stroke.

Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.

BACKGROUND: Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive. METHODS: The expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting. RESULTS: SNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects. CONCLUSION: Our data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.