lncRNA Small Nucleolar RNA Host Gene 1 Research Articles

LncRNA SNHG12 regulates gastric cancer progression by acting as a molecular sponge of miR‑320.

Gastric cancer (GC) is one of the most common malignancies worldwide. Previous studies have focused on long non‑coding RNAs (lncRNAs), which have important roles in the development and progression of GC. The present study aimed to clarify the expression and function of lncRNA small nucleolar RNA host gene 12 (SNHG12) in GC. The expression and the clinical characteristics of GC were analyzed in the samples from patients with GC and matched adjacent normal tissues. The present study determined that SNHG12 was significantly overexpressed in GC and its expression level was highly associated with tumor size, tumor‑node‑metastasis stage, distant metastasis, lymphatic metastasis. Patients with high SNHG12 expression had a short survival period. Additionally, inhibition of SNHG12 in GC cell lines SGC‑7901 and AGS suppressed cell growth, colony formation, proliferation and invasion. MicroRNA (miR)‑320, a putative target gene of SNHG12, was inversely correlated with SNHG12 expression in GC tissues and cell lines. In addition, the present study determined that miR‑320 was directly regulated by SNHG12 and suppression of miR‑320 expression reversed the inhibitory effects of SNHG12 siRNA on GC cell proliferation and invasion. These findings revealed that SNHG12 acts as a tumor promoter by directly targeting miR‑320 in GC, suggesting a potential novel biomarker for the diagnosis and prognosis ofGC.

LncRNA SNHG12 contributes to multidrug resistance through activating the MAPK/Slug pathway by sponging miR-181a in non-small cell lung cancer.

Small nucleolar RNA host gene 12 (SNHG12), as one of the long non-coding RNAs (lncRNAs), plays an oncogenic role in various cancers, however, its role in the chemoresistance of non-small cell lung cancer (NSCLC) is unclear. In this study, we investigated the effect of SNHG12 on multidrug resistance (MDR) in NSCLC. The results showed that SNHG12 was high-expressed and miR-181a was low-expressed in NSCLC tumor tissues and cell lines. Knockdown of SNHG12 reversed the resistance to cisplatin, paclitaxel and gefitinib in A549/DDP, A549/PTX and PC9/AB2 cells through inducing cell apoptosis. Moreover, SNHG12 silencing suppressed MAPK1 and MAP2K1 expression by upregulating miR-181a, leading to inhibition of the MAPK/Slug pathway through decreasing phosphorylated MAPK1 (p-MAPK1), phosphorylated MAP2K1 (p-MAP2K1) and Slug levels. Furthermore, downregulation of SNHG12 enhanced the sensitivity of NSCLC cells to cisplatin in nude mice. Overall, our study is the first to identify a SNHG12-miR-181a-MAPK/Slug axis to elucidate in part how SNHG12 exert functions in NSCLC MDR, providing a novel therapeutic target to overcome MDR in NSCLC.

LncRNA SNHG15 contributes to proliferation, invasion and autophagy in osteosarcoma cells by sponging miR-141

BackgroundLncRNA small nucleolar RNA host gene 15 (SNHG15) was reported to play an oncogenic role in tumors. However, the role of SNHG15 and its molecular mechanism in osteosarcoma (OS) cells are largely unknown.MethodsqRT-PCR was performed to evaluate the expression levels of SNHG15 and miR-141 in OS tissues and cells. Cell transfection with different siRNAs, miRNAs or pcDNAs into U2OS and MG63 cells were carried out by Lipofectamine 2000. The effects of SNHG15 and miR-141 on OS cell proliferation, invasion and the levels of autophagy-related proteins were analyzed by MTT assay, Transwell invasion/migration assay and western blot, respectively. Luciferase reporter assay was used to confirm whether SNHG15 could directly interact with miR-141.ResultsWe found that up-regulation of SNHG15 was inversely correlated with miR-141 expression in OS tissues. SNHG15 knockdown and miR-141 overexpression significantly suppressed cell proliferation, invasion, migration and autophagy while SNHG15 overexpression and miR-141 repression exhibited the opposite effects on OS cells. Besides, SNHG15 could directly interact with miR-141 and regulate its expression. Furthermore, miR-141 suppressing significantly overturned the inhibition on proliferation, invasion, migration and autophagy mediated by SNHG15 knockdown while miR-141 overexpression remarkably attenuated SNHG15 overexpression-induced proliferation, invasion, migration and autophagy in OS cells.ConclusionOur data showed that SNHG15 contributes to proliferation, invasion, migration and autophagy in OS by negatively regulating miR-141, providing a new potential target and prognostic biomarker for the treatment of OS.

Therapy Decisions for Patients with High-Grade Glioma and Their Families

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.

LncRNA SNHG6 is Associated with Poor Prognosis of Gastric Cancer and Promotes Cell Proliferation and EMT through Epigenetically Silencing p27 and Sponging miR-101-3p

Background/Amis: Long non-coding RNAs (lncRNAs), a novel class of transcripts, have been shown to play critical roles in diverse cellular biological processes, including tumorigenesis. Small nucleolar RNA host gene 6 (SNHG6) regulates various biological processes in cancer cells. However, the biological role of SNHG6 in gastric cancer still remains to be explored. The aim of this study is to investigate the characteristic of the SNHG6 in gastric cancer. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of SNHG6 in gastric cancer tissues and cell lines. MTT assays, colony formation assays were used to determine the impact of SNHG6 on tumorigenesis . Flow cytometric analysis of cell cycle and apoptosis was performed to measure the effect of SNHG6 on cell cycle and apoptosis rate. Transwell assay was performed to measure the effect of SNHG6 on cell migration. Western blotting and immunofuorescence were utilized to examine the effect of SNHG6 on epithelial-mesenchymal transition (EMT) of GC cells. Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), RNA-pulldown and luciferase reporter assays were employed to dissect molecular mechanisms. Results: In this study, we revealed that SNHG6 was overexpressed in gastric cancer tissues and cell lines. High expression levels of SNHG6 wereassociated with invasion depth, lymph node metastasis, distant metastasis and tumor/node/metastasis (TNM) stage, and predicted poor prognosis. Loss-of-function assays revealed that silenced SNHG6 obviously inhibited gastric cancer cell growth, weakened cell migration capacity and suppressed the EMT processes of gastric cancer cells. Additionally, ChIP, RIP, RNA-pulldown and luciferase reporter assays evidenced that SNHG6 could epigenetically silenced p27 and could competitively sponging miR-101-3p thereby regulating zinc finger E-box-binding homeobox 1 (ZEB1). Conclusion: In summary, our findings demonstrated that SNHG6 acted as an oncogene in gastric cancer cells through regulating miR-101-3p/ZEB1 at a post-transcriptional level and silencing expression at a transcriptional level by recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p27. SNHG6 might serve as a candidate prognostic biomarker and a target for novel therapies of gastric cancer patients.

LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells.

Several long non-coding RNA (lncRNA) might be correlated with the prognosis of colorectal cancer (CRC) and serve as a diagnostic and prognostic biomarker. However, the exact expression pattern of small nucleolar RNA host gene 12 (SNHG12) in colorectal cancer and its clinical significance remains unclear. The level of SNHG12 was detected by qRT-PCR in CRC tissues and CRC cells. MTT assay and colony formation assay were performed to examine the cell proliferation of CRC cells transfected with pcDNA-SNHG12 or si-SNHG12. Flow cytometry technology was used to detect cell cycle and cell apoptosis of CRC cells transfected with pcDNA-SNHG12 or si-SNHG12. The protein level of cell cycle progression-related molecules, including cyclin-dependent kinases (CDK4, CDK6), cyclin D1 (CCND1) and cell apoptosis-related molecule caspase 3 was detected by western blot. The effect of SNHG12 knockdown was examined in vivo. Increased levels of SNHG12 were observed in CRC tissues and in CRC cells. SNHG12 promoted the cell proliferation of CRC cells. In addition, SNHG12 overexpression boosted the cell cycle progression of SW480 cells transfected with pcDNA-SNHG12 and SNHG12 knockdown inhibited the cell cycle progression of HT29 cells transfected with si-SNHG12. SNHG12 also inhibited the cell apoptosis of CRC cells. We also found that SNHG12 increased the expression of cell cycle-related proteins and suppressed the expression of caspase 3. Our results suggest that SNHG12 promoted cell growth and inhibited cell apoptosis in CRC cells, indicating that SNHG12 might be a useful biomarker for colorectal cancer.

Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes cell proliferation and migration by upregulating angiomotin gene expression in human osteosarcoma cells.

The long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) has a role in cell proliferation and migration. Angiomotin, encoded by the AMOT gene, is a protein that regulates the migration and organization of endothelial cells. SNHG12 and AMOT have been shown to play a role in a variety of human cancers but have yet to be studied in detail in human osteosarcoma. Tissue samples from primary osteosarcoma (n = 20) and adjacent normal tissues (n = 20), the osteosarcoma cell lines, SAOS-2, MG-63, U-2 OS, and the human osteoblast cell line hFOB (OB3) were studied using Western blot for angiomotin, and quantitative real-time polymerase chain reaction for the expression of SNHG12 and AMOT. The expression of SNHG12 was knocked down using RNA interference. Cell migration assays were performed. Cell apoptosis was studied using flow cytometry. SNHG12 and AMOT messenger RNA (mRNA) expression was upregulated in osteosarcoma tissues and cell lines when compared with normal tissues and cells. Upregulation of AMOT mRNA was associated with upregulation of SNHG12. Knockdown of SNHG12 reduced the expression of angiomotin in osteosarcoma cells and suppressed cell proliferation and migration but did not affect cell apoptosis. This preliminary study has shown that the lncRNA SNHG12 promotes cell proliferation and migration by upregulating AMOT gene expression in osteosarcoma cells in vivo and in vitro. Further studies are recommended to investigate the role of SNHG12 and AMOT expression in tumor cell proliferation and migration and angiogenesis in osteosarcoma and a range of malignant mesenchymal tumors.