Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

Ren, Shi‐Bin; Liu, Jiuzhou; Feng, Yun; Li, Zhenyu; He, Liang; Li, Leilei; Cao, Xiaozhong; Wang, Zhenghua; Zhang, Yanwu

doi:10.1186/s13046-019-1398-2

Cited by 136 publications

(94 citation statements)

References 33 publications

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“…10 In addition, circDENND4C accelerated glycolysis, migration, and invasion of breast cancer cells under hypoxia by competitively sponging miR-200b/200c. 11 Growing evidence suggests that circRNA promotes various biological behaviors in the development of NSCLC, including proliferation, 12 invasion, 13 migration, 13 and chemoresistance. 14 Therefore, studying the important role of circRNA in tumorigenesis may be effective for identifying novel molecular targets to help inhibit the development of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

Liu¹,

Yang²,

Cao³

et al. 2020

OTT

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Circular RNA (circRNA) is involved in the development of various cancers. However, whether circRNA can inhibit the tumorigenesis of non-small cell lung cancer (NSCLC) is still unclear. We aimed to explore the epigenetic function of tumor-suppressive circRNA (hsa_circ_RNA_0011780) and its downstream regulatory factors in NSCLC. Patients and Methods: Quantitative polymerase chain reaction (qPCR) was used to evaluate hsa_circ_11780 expression in NSCLC tissues and cell lines. The impact of high hsa_circ_11780 expression on overall survival in patients with NSCLC was tested using the Log rank test. The association between decreased hsa_circ_11780 expression and clinicopathological features in patients with NSCLC was analyzed using the Chi-squared test. In vitro cell proliferation and apoptosis were assayed using the cell counting kit-8 (CCK-8) and flow cytometry, respectively. Mice xenograft models were used to determine the tumor promoting effects of hsa_circ_11780 on NSCLC in vivo. The underlying regulatory mechanism was predicted by bioinformatics and verified by a dual-luciferase reporter assay, RNA transfection, qPCR, and Western blotting. The correlation between miR-544a and hsa_-circ_11780 expression was verified using Spearman correlation coefficient. Results: The expression of hsa_circ_11780 in NSCLC tissues and cell lines strongly declined. Low hsa_circ_11780 expression is more likely to present in patients with a large tumor size (>3cm), distant metastasis, and poor overall survival. hsa_circ_11780 overexpression strongly inhibited proliferation, migration, and invasion of NSCLC cells (H226 and A549) in vitro and inhibited tumor growth in vivo. Furthermore, hsa_circ_11780 repressed miR-544a function by competitively binding to the complementary sites of miR-544a. miR-544a released by the declining expression of hsa_circ_11780 reduced the protein concentration of F-Box and WD repeat domain containing 7 (FBXW7) in NSCLC cells. Conclusion: FBXW7 expression mediated by the hsa_circ_11780/miR-544a axis is markedly associated with the proliferation, migration, and invasion of NSCLC, resulting in decreased survival. These findings suggest that this regulatory axis may serve as a novel therapeutic target in NSCLC.

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Section: Introductionmentioning

confidence: 99%

<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

Liu¹,

Yang²,

Cao³

et al. 2020

OTT

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“…Hypoxia-induced overexpression of circDENND2A promotes the migration and invasion of glioma cells by sponging miR-625-5p [95]. In addition, more HRCs, including circRNA_403658, cir-cDENND4C, and circRNA_0000977, have been identified to participate in cancer progression by sponging corresponding miRNAs [29,96,97]. Although limited research has uncovered the role of HRCs, promising functions of circRNAs in human cancers have been preliminarily established, and we believe that HRCs will be the next hotspot in the research field of hypoxia-induced cancer progression.…”

Section: Regulation Of Circrnas By Hif-1αmentioning

confidence: 99%

The interplay between HIF-1α and noncoding RNAs in cancer

Peng

Han

et al. 2020

J Exp Clin Cancer Res

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Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.

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“…Recent studies have found that circRNAs are involved in the development and progression of various cancers [22][23][24], such as gastric cancer, breast cancer, and colorectal cancer. Current evidence suggests that circRNAs can target miRNAs, often referred to as "miRNA sponges, " to reduce the levels of miRNAs and release their targeted inhibition of mRNAs, thereby regulating the expression of protein-coding genes [25][26][27]. These studies have found that circRNAs may play a key role in the development and progression of cancers.…”

Section: Discussionmentioning

confidence: 99%

Construction of a circRNA-miRNA-mRNA network based on competitive endogenous RNA reveals the function of circRNAs in osteosarcoma

Qiu

Chen

et al. 2020

Cancer Cell Int

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Background: Osteosarcoma (OS) is a common primary malignant bone tumour. Growing evidence suggests that circular RNAs (circRNAs) are closely related to the development of tumours. However, the function of circRNAs in OS remains unknown. Here, we aimed to determine the regulatory mechanisms of circRNAs in OS. Methods:The expression profiles of OS circRNA (GSE96964), microRNA (GSE65071) and mRNA (GSE33382) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed circRNAs, miRNAs and mRNAs in OS. A ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. MRNAs with significant prognostic differences were identified by the TARGET database in the network. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs. Results:A total of 15 downregulated circRNAs, 136 upregulated miRNAs and 52 downregulated mRNAs were identified in OS. Finally, a circRNA-miRNA-mRNA network was constructed in OS based on 14 circRNAs, 24 miRNAs, and 52 mRNAs. GO and KEGG pathway analyses suggested that the mRNAs in the network may be involved in the pathogenesis and progression of OS. Four mRNAs identified by the TARGET database were significantly associated with OS survival prognosis. A circRNA-miRNA-mRNA subnetwork was constructed based on these four mRNAs. Conclusion:Our results provide a deeper understanding of the regulatory mechanisms by which circRNAs compete for endogenous RNAs in OS.

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Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

Cited by 136 publications

References 33 publications

<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

The interplay between HIF-1α and noncoding RNAs in cancer

Construction of a circRNA-miRNA-mRNA network based on competitive endogenous RNA reveals the function of circRNAs in osteosarcoma

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