The Emerging Function and Mechanism of ceRNAs in Cancer

Wang, Yunfei; Hou, Jiakai; He, Dandan; Sun, Ming; Zhang, Peng; Yu, Yonghao; Chen, Yiwen

doi:10.1016/j.tig.2016.02.001

Cited by 156 publications

(132 citation statements)

References 132 publications

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“…RNAs, circRNAs included, can serve as ceRNAs and compete binding to shared miRNAs . Due to their stability, predominant cytoplasm localization and the non‐coding nature, circRNAs have advantages as ceRNAs . There are various studies reporting circRNAs acting as ceRNAs to regulate tumour progress .…”

Section: Introductionmentioning

confidence: 99%

circCPA4 acts as a prognostic factor and regulates the proliferation and metastasis of glioma

Peng

Qin

Zhang

et al. 2019

J Cellular Molecular Medi

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Circular RNAs (circRNAs) are reported to play vital roles in tumour process and might be potential prognostic biomarkers and therapeutic targets for tumours. But the expression and function of circRNAs in glioma remain unclear. Here, we performed circRNA microarray analysis of glioma tissues and matched normal brain tissue samples to explore the circRNA profile in glioma. GO analysis, KEGG and Reactom pathway analysis of linear mRNA transcripts corresponding to circRNAs were performed to study the involved biological process and pathways. The clinical significance of the selected circRNA was investigated by Kaplan‐Meier survival analysis. Relevant biological function, such as cell proliferation and metastasis, was detected in vitro and in vivo. And possible mechanism of the regulatory function of the selected circRNA in glioma was explored. We found that circCPA4 (hsa_circ_0082374) up‐regulated the most in glioma tissues and high levels of circCPA4 were positively related to poor outcome of glioma. And knockdown of circCPA4 suppresses cell proliferation and metastasis in glioma. Moreover, circCPA4 interacts with let‐7 and serves as a sponge for let‐7. Through the competitive endogenous RNA (ceRNA) mechanism, circCPA4 sponges let‐7 to regulate the expression of CPA4 and glioma progression. The circCPA4/let‐7/CPA4 axis regulates glioma progression by ceRNA mechanism, and circCPA4 could be a novel prognostic biomarker and target for glioma treatment.

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Section: Introductionmentioning

confidence: 99%

circCPA4 acts as a prognostic factor and regulates the proliferation and metastasis of glioma

Peng

Qin

Zhang

et al. 2019

J Cellular Molecular Medi

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“…Localization of lncRNAs may suggest how lncRNAs exert their functions [28]. LncRNAs localized in the cytoplasm mainly function as a sponge to sequester miRNAs and their target genes [37], while lncRNAs localized in the nucleus may be involved in epigenetic regulation or guide RNA of transcription factors [38]. In this study, we found that LINC01197 is mainly localized in the nucleus but not in the cytoplasm.…”

Section: Discussionmentioning

confidence: 58%

FOXO1-regulated lncRNA LINC01197 inhibits pancreatic adenocarcinoma cell proliferation by restraining Wnt/β-catenin signaling

Jing

Wang

Liu

et al. 2019

J Exp Clin Cancer Res

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Background Recent studies have revealed that numerous oncogenic long non-coding RNAs (lncRNAs) play pivotal roles in pancreatic ductal adenocarcinoma (PDAC) progression, but little is known about tumor-suppressive lncRNAs in PDAC. This study was conducted to evaluate the function of tumor-suppressive LINC01197 in PDAC progression and investigate the detailed mechanisms. Methods LncRNA microarray was used to identify differentially expressed lncRNAs in FOXO1-overexpressing PANC1 cells. LINC01197 expression was evaluated by quantitative PCR, Northern blotting, and fluorescence in situ hybridization. The Cancer Genome Atlas database was used to analyze the prognostic role of LNC01197 in PDAC. A luciferase reporter assay was performed to confirm the interaction between LNC01197 and FOXO1. The biological function of LINC01197 was evaluated by colony formation assay in vitro and in an animal subcutaneous tumorigenesis experiment and Ki67 staining in vivo. RNA-pulldown, western blotting, RNA immunoprecipitation assay, and co-immunoprecipitation were further performed to determine the molecular mechanism of LNC01197 and β-catenin in the Wnt pathway. Results We found that a FOXO1-related lncRNA, LINC01197, was significantly decreased in PDAC malignant tissues and that its low expression predicted poor prognosis. Moreover, LINC01197 was mainly localized in the nucleus and inhibited PDAC cell proliferation both in vitro and in vivo. Mechanistically, LINC01197 was found to bind to β-catenin and inhibit Wnt/β-catenin signaling activity by disrupting β-catenin binding to TCF4 in PDAC cells. Conclusions The novel FOXO1/LINC01197/β-catenin axis was dysregulated during PDAC progression. Our study provides insight into the mechanisms of LINC01197 in PDAC and reveal a potential target for PDAC clinical therapy and prognostic prediction.

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“…The past decades have witnessed systematic efforts to provide novel insights into the impacts of genetic factors on osteosarcoma, which are mainly involved in coding genes or miRNAs. 34,35 Systematic analysis of ceRNA-mediated regulatory network has been carried out in hepatocellular cancer, 10 pancreatic cancer, 11 and bladder cancer, 12 but few in osteosarcoma. 33 Recent studies 6,7 indicate that lncRNAs could function as ceRNAs to indirectly regulate mRNAs by competing for shared miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA MEG3 play an important role in osteosarcoma development through sponging microRNAs

Jiang

Zhou

et al. 2018

J of Cellular Biochemistry

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More and more evidence indicate long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) to indirectly regulate messenger RNAs (mRNAs) by acting as microRNA (miRNA) sponges, which represents a novel layer of gene regulation that plays a critical role in the development of cancers. However, functional roles and regulatory mechanisms of lncRNA‐mediated ceRNAs network in osteosarcoma are still largely unknown. Here, we comprehensively compared the expression profiles of mRNAs, lncRNAs, and miRNAs between osteosarcoma and normal samples from the Gene Expression Omnibus (GEO) to elaborate related latent mechanisms. Two lncRNAs, ie, LINC01560 and MEG3, were identified to be aberrantly expressed. Importantly, MEG3 was considered as a promising diagnostic biomarker and therapeutic target for patients with osteosarcoma according to the Kaplan‐Meier analysis of another independent osteosarcoma data set from the Cancer Genome Atlas (P = 0.05). Eventually, we successfully established a dysregulated lncRNA‐related ceRNA network, including one osteosarcoma‐specific lncRNA, three miRNAs and four mRNAs. In conclusion, this study should be beneficial for improving our understanding of the lncRNA‐mediated ceRNA regulatory mechanisms in the pathogenesis of osteosarcoma and providing it with novel candidate diagnostic and therapeutic biomarkers.

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The Emerging Function and Mechanism of ceRNAs in Cancer

Cited by 156 publications

References 132 publications

circCPA4 acts as a prognostic factor and regulates the proliferation and metastasis of glioma

circCPA4 acts as a prognostic factor and regulates the proliferation and metastasis of glioma

FOXO1-regulated lncRNA LINC01197 inhibits pancreatic adenocarcinoma cell proliferation by restraining Wnt/β-catenin signaling

Long noncoding RNA MEG3 play an important role in osteosarcoma development through sponging microRNAs

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