Dataset Information

The positive feedback loop of lncRNA DANCR/miR-138/Sox4 facilitates malignancy in non-small cell lung cancer.

ABSTRACT: Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide. The abnormal expression of long non-coding RNAs (lncRNAs) has been reported to be closely associated with the progression of human cancers, including NSCLC. Here, we demonstrated that differentiation antagonizing noncoding RNA (DANCR) was overexpressed in NSCLC tissues. Upregulation of DANCR expression was significantly associated with larger tumor size, advanced TNM stage and lymph node metastasis, and also predicted poor prognoses of patients with NSCLC. Functional experiments showed that DANCR enhanced NSCLC growth and metastasis both in vitro and in vivo. Further investigation revealed that DANCR could compete with the Sox4 mRNA to bind with miR-138, thus affecting Sox4 expression. In addition, we found that Sox4 bound to the promoter regions of DANCR gene to activate DANCR expression, suggesting a positive feedback loop of DANCR/miR-138/Sox4 in NSCLC. Taken together, these results provide a comprehensive analysis of the roles of DANCR as a competing endogenous RNA (ceRNA) in NSCLC progression.

SUBMITTER: Bai Y

PROVIDER: S-EPMC6405976 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The positive feedback loop of lncRNA DANCR/miR-138/Sox4 facilitates malignancy in non-small cell lung cancer.

Bai Yong Y Zhang Guojun G Chu Heying H Li Ping P Li Juan J

American journal of cancer research 20190201 2

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide. The abnormal expression of long non-coding RNAs (lncRNAs) has been reported to be closely associated with the progression of human cancers, including NSCLC. Here, we demonstrated that differentiation antagonizing noncoding RNA (DANCR) was overexpressed in NSCLC tissues. Upregulation of DANCR expression was significantly associated with larger tumor size, advanced TNM stage and lymph node metastasis, and also predic ...[more]

PMID: 30906628

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Project description:BackgroundAngiogenesis plays a critical role in the progression of glioma. Previous studies have indicated that RNA-binding proteins (RBPs) interact with RNAs and participate in the regulation of the malignant behaviors of tumors. As a type of endogenous non-coding RNAs, circular RNAs (circRNAs) are abnormally expressed in various cancers and are involved in diverse tumorigeneses including angiogenesis.MethodsThe expression levels of FUS, circ_002136, miR-138-5p, SOX13, and SPON2 were determined using quantitative real-time PCR (qRT-PCR) and western blot. Transient cell transfection was performed using the Lipofectamine 3000 reagent. The RNA-binding protein immunoprecipitation (RNA-IP) and the RNA pull-down assays were used to detect the interaction between FUS and circ_002136. The dual-luciferase reporter assay system was performed to detect the binding sites of circ_002136 and miR-138-5p, miR-138-5p and SOX13. The chromatin immunoprecipitation (ChIP) assays were used to examine the interactions between transcription factor SOX13 and its target proteins .ResultsWe demonstrated that down-regulation of FUS or circ_002136 dramatically inhibited the viability, migration and tube formation of U87 glioma-exposed endothelial cells (GECs). MiR-138-5p was down-regulated in GECs and circ_002136 functionally targeted miR-138-5p in an RNA-induced silencing complex (RISC). Inhibition of circ_002136, combined with the restoration of miR-138-5p, robustly reduced the angiogenesis of GECs. As a target gene of miR-138-5p, SOX13 was overexpressed in GECs and was proved to be involved in circ_002136 and miR-138-5p-mediated angiogenesis in gliomas. In addition, we found that SOX13 was directly associated with and activated the SPON2 promoter, thereby up-regulating the expression of SPON2 at the transcriptional level. Knockdown of SPON2 suppressed the angiogenesis in GECs. More important, SOX13 activated the FUS promoter and increased its expression, forming a feedback loop.ConclusionOur data suggests that the feedback loop of FUS/circ_002136/miR-138-5p/SOX13 played a crucial role in the regulation of angiogenesis in glioma. This also provides a potential target and an alternative strategy for combined glioma therapy.

Project description:Background: Pancreatic cancer is a malignancy with poor prognosis. Importin 7 (IPO7) is a soluble nuclear transport factor, which has been linked to the pathogenesis of several human diseases. However, its role and underlying mechanism in pancreatic cancer are still obscure. Methods: Immunohistochemical staining and quantitative real-time polymerase chain reaction (qPCR) were performed to determine IPO7 expression in pancreatic cancer tissues and adjacent tissues. Western blot was used to measure IPO7 expression at the protein level in cell lines. Cell Counting Kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU), flow cytometry, and Transwell assays were employed to explore the biological functions of IPO7. Subcutaneous xenograft transplanted tumor model and caudal vein injection model in mice were also established to validate the oncogenic role of IPO7. Western blot and qPCR were utilized to detect the regulatory function of IPO7 on p53 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), respectively. Interaction between MALAT1 and miR-129-5p and interaction between miR-129-5p and IPO7 were verified by bioinformatics prediction, qPCR, dual-luciferase reporter gene experiment, RNA immunoprecipitation (RIP), and pull-down assay. Results: Upregulation of IPO7 in pancreatic cancer tissues was associated with adverse prognosis of the patients with pancreatic cancer. Knocking down IPO7 remarkably suppressed cancer cell proliferation and metastasis, while it promoted apoptosis. Overexpression of IPO7 facilitated the malignant phenotypes of pancreatic cancer cells. Mechanistically, IPO7 could repress the expression of p53 and induce the expression of MALAT1 but reduce miR-129-5p expression. Furthermore, miR-129-5p was identified as a posttranscriptional regulator for IPO7, and its inhibition led to IPO7 overexpression in pancreatic cancer cells. Conclusion: IPO7 is a novel oncogene for pancreatic cancer, and IPO7/p53/MALAT1/miR-129-5p positive feedback loop facilitates the progression of this deadly disease.

Dataset Information

The positive feedback loop of lncRNA DANCR/miR-138/Sox4 facilitates malignancy in non-small cell lung cancer.

Publications

The positive feedback loop of lncRNA DANCR/miR-138/Sox4 facilitates malignancy in non-small cell lung cancer.

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