Long non-coding RNA SNHG1 promotes bladder cancer progression by upregulating EZH2 and repressing KLF2 transcription

Abstract Objective: Long Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression. Method: The expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established. Results: SNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription. Conclusion: Our study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.

SNHG1 promotes MPP+-induced cytotoxicity by regulating PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells via sponging miR-153-3p

BACKGROUND: Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson's disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. Methods: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis. RESULTS: Increased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p. CONCLUSION: SNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.

Expression level of lncRNA SNHG1 in endometrial cancer tissues and its clinical significance / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the expression level of lncRNA (long non-coding RNA) SNHG1 in endometrial cancer tissues, and to analyze its mechanism of action as well as its clinical significance. Methods: NCBI-GEO and TCGA database were used to analyze the expression level of SNHG1 in endometrial cancer. A total of 53 cases of endometrial cancer tissue samples and 41 cases of normal endometrial tissue samples were collected from January 2016 to March 2019 at Zhongxin Ecocity Hospital of Tianjin Medical University; in addition, endometrial cancer cell lines Ishikawa and HEC-1A as well as normal endometrial ESC cells were also collected for this study. qPCR was used to detect the expression level of SNHG1 in tissues and cells, and its correlation with the clinical characteristics of patients were statistically analyzed. The effect of SNHG1 on cell proliferation and apoptosis of HEC-1A cells was measured by MTT assay and Annexin V/PI double staining Flow cytometry, respectively. The migration and invasion of HEC-1A cells were measured by Transwell assay. StarBase was used to predict the regulatory relationship between SNHG1 and RELA, which was then verified by qPCR and Western blotting. Dual fluorescent reporter gene system and qPCR were adopted to identify the influence of SNHG1 on NF-κB pathway. Results: The expression of SNHG1 was significantly up-regulated in endometrial cancer tissues compared with normal endometrial tissues (P<0.01), and its expression was related to tumor size, TNM staging, histological grade and lymph node metastasis (all P<0.05). The expression level of SNHG1 in Ishikawa and HEC-1A cells was significantly higher than that in ESC cells (all P<0.01). Overexpression of SNHG1 notably promoted the proliferation, migration and invasion and inhibited cell apoptosis of HEC-1A cells. By promoting the expression of RELA, SNHG1 activated the NF-κB pathway and promoted the expressions of downstream gene IL-6 and CCL19 (all P<0.01). Conclusion: Up-regulated SNHG1 in endometrial cancer functions as an oncogene by activating the NF-κB pathway through promoting the RELA expression.