Dataset Information

Silencing of Long Non-Coding RNA-HCG18 Inhibits the Tumorigenesis of Gastric Cancer Through Blocking PI3K/Akt Pathway.

ABSTRACT: Purpose:Long non-coding RNAs (lncRNAs) play critical regulatory roles in the tumorigenesis of GC. This study aimed to investigate the regulatory effect and mechanism of lncRNA-HCG18 on GC. Methods:The expression of lncRNA-HCG18 was detected in GC tissues and cell lines by qRT-PCR. LncRNA-HCG18 was silenced in AGS and MGC803 cells by the transfection of lncRNA-HCG18 siRNA (si-HCG18). MTT, transwell and Annexin V-PI double staining assay were performed to assess the proliferation, migration, invasion and apoptosis of GC cells. The expression of PI3K/Akt pathway-, apoptosis-, and migration-related proteins were detected by Western blot. An activator of PI3K/Akt pathway 740 Y-P was used to activate the PI3K/Akt pathway in AGS cells. A human tumor xenograft model was established in mice to evaluate the effects of si-HCG18 in vivo. Results:LncRNA-HCG18 was overexpressed in GC tissues and cells. Up-regulation of lncRNA-HCG18 was positively correlated with the stage of tumor node metastasis and invasion depth. Silencing of lncRNA-HCG18 suppressed the proliferation, migration and invasion, and induced the apoptosis of GC cells. Silencing of lncRNA-HCG18 blocked the PI3K/Akt pathway. The intervention of 740Y-P reversed the anti-tumor effect of lncRNA-HCG18 on GC cells. In addition, silencing of lncRNA-HCG18 suppressed the growth of GC xenografts in mice. Conclusion:Silencing of lncRNA-HCG18 inhibited the tumorigenesis of GC through blocking the PI3K/Akt pathway, suggesting a novel therapeutic target for GC.

SUBMITTER: Ma F

PROVIDER: S-EPMC7092690 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Silencing of Long Non-Coding RNA-HCG18 Inhibits the Tumorigenesis of Gastric Cancer Through Blocking PI3K/Akt Pathway.

Ma Fengzhen F An Kexiang K Li Yuqin Y

OncoTargets and therapy 20200318

<h4>Purpose</h4>Long non-coding RNAs (lncRNAs) play critical regulatory roles in the tumorigenesis of GC. This study aimed to investigate the regulatory effect and mechanism of lncRNA-HCG18 on GC.<h4>Methods</h4>The expression of lncRNA-HCG18 was detected in GC tissues and cell lines by qRT-PCR. LncRNA-HCG18 was silenced in AGS and MGC803 cells by the transfection of lncRNA-HCG18 siRNA (si-HCG18). MTT, transwell and Annexin V-PI double staining assay were performed to assess the proliferation, m ...[more]

PMID: 32256081

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Project description:BackgroundGlioblastoma is the most common primary malignant intracranial tumor with poor clinical prognosis in adults. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) function as important regulators in cancer progression, including glioblastoma. Here, we identified a new lncRNA LPP antisense RNA-2 (LPP-AS2) and investigated its function and mechanism in the development of glioma.MethodsHigh-throughput RNA sequencing was performed to discriminate differentially expressed lncRNAs and mRNAs between glioma tissues and normal brain tissues. Expression of LPP-AS2, epidermal growth factor receptor (EGFR) and miR-7-5p in glioma tissues and cell lines was detected by real-time quantitative PCR (RT-qPCR), and the functions of lncRNA LPP-AS2 in glioma were assessed by in vivo and in vitro assays. Insight into the underlying mechanism of competitive endogenous RNAs (ceRNAs) was obtained via bioinformatic analysis, dual luciferase reporter assays, RNA pulldown assays, RNA immunoprecipitation (RIP) and rescue experiments.ResultsThe results of high-throughput RNA-seq indicated lncRNA LPP-AS2 was upregulated in glioma tissues and further confirmed by RT-qPCR. Higher LPP-AS2 expression was related to a poor prognosis in glioma patients. Based on functional studies, LPP-AS2 depletion inhibited glioma cell proliferation, invasion and promoted apoptosis in vitro and restrained tumor growth in vivo, overexpression of LPP-AS2 resulted in the opposite effects. In addition, LPP-AS2 and EGFR were observed in co-expression networks. LPP-AS2 was found to function as a ceRNA to regulate EGFR expression by sponging miR-7-5p in glioma cells. The result of chromatin immunoprecipitation (ChIP) assays validated that c-MYC binds directly to the promoter region of LPP-AS2. As a downstream protein of EGFR, c-MYC was modulated by LPP-AS2 and in turn enhanced LPP-AS2 expression. Thus, lncRNA LPP-AS2 promoted glioma tumorigenesis via a miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop.ConclusionsOur study elucidated that LPP-AS2 acted as an oncogene through a novel molecular pathway in glioma and might be a potential therapeutic approach for glioma diagnosis, therapy and prognosis.

Project description:BackgroundPhosphatase and tensin homolog (PTEN) is an important tumor suppressor gene, and its encoded protein has activities of both a protein phosphatase and a lipid phosphatase. However, the substitution effect of protein phosphatase activity remains unclear. PI3K/Akt is the most common pathway negatively regulated by PTEN. The Hippo and PI3K/Akt pathways have a joint effect in regulating cell proliferation and apoptosis. Therefore, how PTEN lipid phosphatase inactivation contributes to the occurrence and development of gastric cancer and the potential role of the Hippo and PI3K/Akt pathways in PTEN lipid phosphatase inactivation mediated gastric tumorigenesis remain to be explored.MethodsImmunohistochemical staining was performed to detect the expression of p-PTEN and YAP in a gastric cancer tissue microarray. Stable cell lines expressing a wild-type or dominant-negative mutant PTEN were established. The proliferation and migration of stable cells were detected by MTT, BrdU, and colony-formation, transwell assay and high content analysis in vitro, and tumor growth differences were observed in xenograft nude mice. Changes in the expression of key molecules in the Hippo and Akt signaling pathways were detected by western blot. Nuclear-cytoplasm separation, immunofluorescence and coimmunoprecipitation analyses were conducted to explore the dysregulation of Hippo in the stable cell lines.ResultsPTEN lipid phosphatase inactivation strongly promoted the proliferation and migration of gastric cancer cells in vitro and tumor growth in vivo. A immunohistochemical analysis of gastric cancer tissues revealed a significant correlation between phosphorylated PTEN and nuclear YAP expression, and both were determined to be independent prognostic factors for gastric cancer. Mechanistically, PTEN lipid phosphatase inactivation abolished the MOB1-LATS1/2 interaction, decreased YAP phosphorylation and finally promoted YAP nuclear translocation, which enhanced the synergistic effect of YAP-TEAD, thus inducing cell proliferation and migration. Moreover, PTEN lipid phosphatase inactivation promoted the PI3K/Akt pathway, and disruption of YAP-TEAD-driven transcription decreased the activation of Akt in a dose-dependent manner.ConclusionsTaken together, our findings indicate that PTEN lipid phosphatase inactivation links the Hippo and PI3K/Akt pathways to promote gastric tumorigenesis and cancer development.

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Silencing of Long Non-Coding RNA-HCG18 Inhibits the Tumorigenesis of Gastric Cancer Through Blocking PI3K/Akt Pathway.

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Silencing of Long Non-Coding RNA-HCG18 Inhibits the Tumorigenesis of Gastric Cancer Through Blocking PI3K/Akt Pathway.

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