The mechanism and function of circular RNAs in human diseases

Lei, Kexin; Bai, Hetian; Wei, Zihao; Xie, Changqing; Wang, Jiongke; Li, Jing; Chen, Qianming

doi:10.1016/j.yexcr.2018.05.002

Cited by 89 publications

(68 citation statements)

References 115 publications

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“…CircRNAs, which lacked 5ʹ-caps and 3ʹ-polyadenylated tails, was first put forward by Sanger and had been ignored in traditional transcriptome studies for decades. 21 Particularly, with next-generation sequencing and computational biology methods developed, a great deal of circRNAs was identified and found to play significant roles in multiple tissues and cells. 22 Nowadays, exploring the underlying mechanisms and functions of circRNAs has attracted more and more attention.…”

Section: Discussionmentioning

confidence: 99%

<p>Identification of circRNA-miRNA-mRNA Networks for Exploring the Fundamental Mechanism in Lung Adenocarcinoma</p>

Liang¹,

Zhang²,

Zhang³

et al. 2020

OTT

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Background: Circular RNAs (circRNAs) were elucidated to act as competing endogenous RNAs (ceRNAs) and to play significant roles in cancer initiation and progression. We aimed to identify the important circRNAs in lung adenocarcinoma and intended to predict the functions of them via the bioinformatics analysis. Methods: We extracted data from three Gene Expression Omnibus (GEO) datasets, GSE101586, GSE101684, and GSE104854, and identified the common differentially expressed circRNAs. Agarose gel electrophoresis and Sanger sequencing were used to verify these significant circRNAs. Then, qRT-PCR was performed to validate the expression through matched tissues and cell lines. Afterwards, a ceRNA network was constructed and functional analysis was performed to predict the potential mechanisms of circRNAs. Results: Five circRNAs (hsa_circ_0072088, hsa_circ_0082564, hsa_circ_0008274, hsa_-circ_0000519 and hsa_circ_0003528) were identified differentially expressed in the three datasets. Following the Agarose gel electrophoresis and qRT-PCR validation, hsa_circ_0072088 and hsa_-circ_0008274 were chosen for further analysis. A ceRNA network of hsa_circ_0072088 and hsa_circ_0008274 was built based on the CSCD/TargetScan/MiRTarbase/StarBase 3.0. Then, the functional analysis showed that several meaningful terms were identified, such as "epithelial to mesenchymal transition (EMT)", "Cellular response to TGF-β stimulus", "MAPK signaling pathway", and "PI3K-AKT signaling pathway". Finally, several significant circRNA/miRNA/mRNA regulatory axes, which were predicted relating to cancer progress, were noted from the network. Conclusion: We identified significant circRNAs and meaningful circRNA-miRNA-mRNA networks to provide novel insight into pathogenesis and therapy of lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

<p>Identification of circRNA-miRNA-mRNA Networks for Exploring the Fundamental Mechanism in Lung Adenocarcinoma</p>

Liang¹,

Zhang²,

Zhang³

et al. 2020

OTT

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“…miRNAs are testified to regulate cell activation, proliferation, and differentiation processes [15, 16]. It is worth noting that the miRNA regulation network is complex, since one miRNA can regulate hundreds of genes and one gene can be targeted by multiple miRNAs.…”

Section: Discussionmentioning

confidence: 99%

MiR-202-5p Promotes M2 Polarization in Allergic Rhinitis by Targeting MATN2

Wang¹,

Liu²,

Song³

et al. 2018

Int Arch Allergy Immunol

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Background: The aim of this study was to investigate the effect of MiR-202-5p on macrophages involved in allergic rhinitis. Methods: Thirty allergic rhinitis patients and 10 healthy controls were recruited. Nasal lavage was utilized to collect mucosal tissues and mucus-derived macrophages. Flow cytometry was used to detect and sort type 2 macrophages, and qRT-PCR and Western blot were adopted to determine the expression of miR-202-5p and MATN2. Luciferase reporter assay and biotin-RNA pulldown were performed to testify the direct binding of miR-202-5p with MATN2. MATN2 was further overexpressed to test its effect on M2 polarization. Results: miR-202-5p, which can promote M2 polarization, was highly expressed in allergic rhinitis mucosal tissues and macrophages compared with the healthy controls. MATN2 could be directly targeted by miR-202-5p and can reverse miR-202-5p-mediated M2 phenotype polarization in allergic rhinitis. Conclusions: miR-202-5p could target MATN2 to induce M2 polarization involved in allergic rhinitis.

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“…SOX5 is a representative of the SOX family which could drive the malignancy of lung cancer, including NSCLC . It has been documented that the competing endogenous RNA (ceRNA) network is a crucial mechanism underlying circRNA in human diseases by sponging miRNA to target mRNA . Interestingly, it has been predicted there were the same complementary sites of miR‐219a‐5p between circCDR1as and SOX5, indicating that circCDR1as might act as a ceRNA for miR‐219a‐5p to derepress SOX5.…”

Section: Introductionmentioning

confidence: 99%

CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

Zhang

Pan

et al. 2020

Thoracic Cancer

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Background Circular RNAs (circRNAs) participate in the development of human cancers by regulating multiple cell processes. CircRNA antisense to the cerebellar degeneration‐related protein 1 transcript (circCDR1as) expression is dysregulated in many cancers, including non‐small‐cell lung cancer (NSCLC). However, the mechanism by which circCDR1as mediates the development of NSCLC remains unknown. Methods A total of 30 paired cancer and normal tissues were collected from patients with NSCLC. The expression levels of circCDR1as, microRNA (miR)‐219a‐5p and Sex determining region Y‐box protein 5 (SOX5) were measured in tissues or cells by quantitative real‐time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide, colony formation, flow cytometry and transwell assays, respectively. The target relationship between miR‐219a‐5p and circCDR1as or SOX5 was validated by dual‐luciferase reporter assay. Results CircCDR1as expression was elevated in NSCLC tissues and cells in comparison to the matched controls. Interference of circCDR1as led to obvious inhibition of cell viability, migration and invasion and increase of apoptosis in NSCLC cells. MiR‐219a‐5p acted as a target of circCDR1as and miR‐219a‐5p downregulation attenuated the regulatory effect of circCDR1as silencing on NSCLC progression. Moreover, miR‐219a‐5p targeted SOX5 to repress the progression of NSCLC in vitro. Besides, circCDR1as knockdown reduced the expression of SOX5 by increasing miR‐219a‐5p level. Conclusion Knockdown of circCDR1as inhibited the progression of NSCLC by decreasing cell viability, migration and invasion and increasing apoptosis by upregulating miR‐219a‐5p and downregulating SOX5.

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The mechanism and function of circular RNAs in human diseases

Cited by 89 publications

References 115 publications

<p>Identification of circRNA-miRNA-mRNA Networks for Exploring the Fundamental Mechanism in Lung Adenocarcinoma</p>

<p>Identification of circRNA-miRNA-mRNA Networks for Exploring the Fundamental Mechanism in Lung Adenocarcinoma</p>

MiR-202-5p Promotes M2 Polarization in Allergic Rhinitis by Targeting MATN2

CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

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