Dataset Information

The long non-coding RNA CRNDE acts as a ceRNA and promotes glioma malignancy by preventing miR-136-5p-mediated downregulation of Bcl-2 and Wnt2.

ABSTRACT: The colorectal neoplasia differentially expressed (CRNDE) gene encodes a long non-coding RNA (lncRNA) that is the most unregulated among 129 lncRNAs differentially expressed in gliomas. In this study, we confirmed high CRNDE expression in clinical glioma specimens and observed through experiments in human glioma cell lines a novel molecular mechanism by which CRNDE may contribute to glioma pathogenesis. By inducing or silencing CRNDE expression, we detected a positive correlation between CRNDE levels and the proliferative, migratory, and invasive capacities of glioma cells, which were concomitant with a decreased apoptosis rate. Our experiments also suggest that these effects are mediated by downregulation of miR-136-5p, which correlated with the glioma WHO grade. Based on predicted CRNDE/miR-136-5p/mRNA interactions, both the mRNA and protein expression analyses suggested that miR-136-5p-mediated repression of Bcl-2 and Wnt2 underlies the pro-tumoral actions of CRNDE. We therefore propose that CRNDE functions as a competing endogenous RNA (ceRNA) that binds to and negatively regulates miR-136-5p, thereby protecting Bcl-2 and Wnt2 from miR-136-5p-mediated inhibition in glioma.

SUBMITTER: Li DX

PROVIDER: S-EPMC5675701 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The long non-coding RNA CRNDE acts as a ceRNA and promotes glioma malignancy by preventing miR-136-5p-mediated downregulation of Bcl-2 and Wnt2.

Li Dong-Xue DX Fei Xiao-Rui XR Dong Yong-Fei YF Cheng Chuan-Dong CD Yang Yang Y Deng Xue-Fei XF Huang Hai-Liang HL Niu Wan-Xiang WX Zhou Chen-Xu CX Xia Cheng-Yu CY Niu Chao-Shi CS

Oncotarget 20171004 50

The colorectal neoplasia differentially expressed (CRNDE) gene encodes a long non-coding RNA (lncRNA) that is the most unregulated among 129 lncRNAs differentially expressed in gliomas. In this study, we confirmed high CRNDE expression in clinical glioma specimens and observed through experiments in human glioma cell lines a novel molecular mechanism by which CRNDE may contribute to glioma pathogenesis. By inducing or silencing CRNDE expression, we detected a positive correlation between CRNDE l ...[more]

PMID: 29152149

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Project description:Long non‑coding RNAs (lncRNAs) and microRNAs (miRNAs) are essential for the progression of tumors, including cutaneous squamous cell carcinoma (CSCC). The present study aimed to examine the competing endogenous RNA (ceRNA) network in CSCC. Differentially expressed genes in CSCC were analyzed using the GSE66359 microarray data set, and the upstream miRNAs and lncRNAs were predicted using online database analysis (TargetScan 7.1, mirDIP 4.1, miRSearch V3.0, miRDB and RNA22 2.0) and were verified in clinical tissues. RNA pull‑down and dual luciferase reporter gene assays were used to verify the targeting relationships among lncRNA human histocompatibility leukocyte antigen complex P5 (HCP5), miR‑138‑5p and enhancer of zeste homolog 2 (EZH2). Cell lines with a high and low HCP5 expression were screened, and a pcDNA‑3.1‑HCP5 overexpression vector, small interfering RNA against HCP5, miR‑138‑5p mimics and miR‑138‑5p inhibitors were transfected into the CSCC cells. Cell viability, invasion, migration, apoptotic rate and autophagy were evaluated. The effects of HCP5 on autophagy and apoptosis of CSCC cells were verified in vivo using Ki67 and TUNEL staining. EZH2 was demonstrated to be upregulated in CSCC cells. miR‑138‑5p target sequences were identified in HCP5 and EZH2. HCP5 was revealed to function as a putative ceRNA of miR‑138‑5p to positively regulate EZH2, and EZH2 was shown to regulate autophagy and apoptosis of CSCC cells through the STAT3/VEGFR2 pathway. HCP5 overexpression decreased miR‑138‑5p levels, increased EZH2 levels and promoted cell malignant behaviors and autophagy but decreased the apoptosis rate. These trends were opposite when HCP5 was silenced. In conclusion, HCP5 may competitively bind to miR‑138‑5p to regulate EZH2 in CSCC cells, promoting autophagy and reducing apoptosis through the STAT3/VEGFR2 pathway. This study may provide a new perspective for understanding the molecular mechanism and treatment of CSCC.

Project description:BACKGROUND:Thyroid carcinoma (TC) is a common malignancy of the endocrine system. This research aimed to examine the expression levels of miR-136-5p and metadherin (MTDH) in TC and unveil their potential targeting relationship. METHODS:TC microRNA (miRNA) microarray and miRNA-sequencing data were collected to evaluated miR-136-5p expression. We assessed the comprehensive expression of miR-136-5p by calculating the standard mean difference (SMD) and summary receiver operating characteristic curves (sROC). Subsequently, the miR-136-5p mimic and inhibitor were transfected into the TC B-CPAP cell, Thiazolyl Blue Tetrazolium Bromide (MTT) assay and cell apoptosis assay by FACS with Annexin V-/7-AAD double staining were performed to explore the biological role of miR-136-5p in the B-CPAP cell line. Prediction of target genes and potential biological function analysis of miR-136-5p were made using miRWalk2.0 and DAVID, respectively. Through target gene prediction, MTDH may be the candidate target gene of miR-136-5p. Subsequently, gene microarrays and RNA-sequencing data were also leveraged for MTDH expression. The meta-analysis method was conducted to evaluate the comprehensive expression level of MTDH. In addition, MTDH protein expression was identified using immunohistochemistry. The MTDH protein levels post-miR-136-5p transfection were verified by western blot, and the dual luciferase reporter assay was adapted to confirm the direct targeting relation between miR-136-5p and MTDH. RESULTS:The miR-136-5p level was remarkably downregulated in TC, the pooled SMD was -0.47 (95% CI: -0.70 to -0.23, I2=36.6%, P=0.192) and the area under the curve (AUC) of the sROC was 0.67 based on 543 cases of TC. MTT indicated that the overexpression of miR-136-5p dramatically inhibited the proliferation of B-CPAP cells. The cell apoptosis increased in the miR-136-5p mimic group compared to the negative control group. In addition, both MTDH mRNA and protein levels were markedly overexpressed, with the pooled SMD being 0.94 (95% CI: -0.35 to 2.24, I2=98.8%, P<0.001), and the AUC of the sROC being 0.85 with 1054 cases of TC. The MTDH protein level was significantly up-regulated in TC than in the non-carcinomic tissues by immunohistochemistry (8.292±1.717 vs. 2.618±2.570, P<0.001). Western blot indicated that MTDH protein expression was suppressed by miR-136-5p mimic in the B-CPAP cell line, which was further supported by the dual luciferase reporter assay. CONCLUSION:The miR-136-5p/MTDH axis may play a vital role in modulating TC tumorigenesis, providing new insight into possible molecular mechanisms of TC oncogenesis.

Dataset Information

The long non-coding RNA CRNDE acts as a ceRNA and promotes glioma malignancy by preventing miR-136-5p-mediated downregulation of Bcl-2 and Wnt2.

Publications

The long non-coding RNA CRNDE acts as a ceRNA and promotes glioma malignancy by preventing miR-136-5p-mediated downregulation of Bcl-2 and Wnt2.

Similar Datasets

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