Emerging Roles of Exosomal Circular RNAs in Cancer

Seimiya, Takahiro; Otsuka, Motoyuki; Iwata, Takuma; Shibata, Chikako; Tanaka, Eri; Suzuki, Tatsunori; Koike, Kazuhiko

doi:10.3389/fcell.2020.568366

Cited by 61 publications

(50 citation statements)

References 80 publications

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“…Emerging reports indicate that circRNAs regulate important functions and are closely correlated with diverse human diseases [15,16]. In our previous study, we had presented the differential circRNA expression pro les in the placenta of FGR fetuses.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0081343 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-210-5p/DLX3 axis

Xie

Wang

Luo

et al. 2021

Preprint

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Background: Various circular RNAs (circRNAs) are dysregulated in the placenta of fetal growth restriction fetuses, but their role and regulatory mechanisms have not been fully elucidated. Herein, we aimed to elucidate the role of hsa_circ_0081343 in regulating the migration, invasion, and apoptosis in the human extravillous trophoblast HTR-8 cells.Methods: circRNA and miRNA levels were examined using quantitative real-time PCR (RT-PCR). Overexpression plasmid constructs and siRNA were used to overexpress and knockdown hsa_circ_0081343, respectively. Transwell assay and flow cytometry analysis were performed to evaluate the effect of hsa_circ_0081343 or miR-210-5p on migration, invasion, and apoptosis. Protein levels were analyzed using western blot. Dual luciferase activity assay and anti-AGO2 RNA immunoprecipitation (RIP) assays were performed to identify the relationship between miR-210-5p and hsa_circ_0081343.Results: Hsa_circ_0081343 expression was significantly downregulated in 37 FGR placental tissues as compared to healthy placental control tissues. Hsa_circ_0081343 overexpression possibly inhibits apoptosis by downregulating the expression of cleaved caspase 3 and caspase 9 and alleviates the migration and invasion of HTR-8 cells by inducing the expression of MMP2 and MMP9. The dual luciferase activity and anti-AGO2 RIP assay results showed that hsa_circ_0081343 binds to miR-210-5p. miR-210-5p overexpression eliminated the effect of hsa_circ_0081343 overexpression in HTR-8 cells. Finally, DLX3 was identified as a direct target of miR-210-5p. Conclusions: Hsa_circ_0081343 regulates the migration, invasion, and apoptosis of HTR-8 cells via the hsa-miR-210-5p/DLX3 axis. Thus, hsa_circ_0081343 plays a key role in the etiology and pathogenesis of FGR implicating its importance as a novel candidate for targeted FGR therapy.

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Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0081343 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-210-5p/DLX3 axis

Xie

Wang

Luo

et al. 2021

Preprint

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“…Besides, miRNA profiles encapsulated into exosomes are prespecified, which refers to the fact that exosomal miRNAs reflect specific information of parental cells. In line with this, accumulating evidence proves exosomal miRNAs as novel biomarkers in early detection, serial monitoring, and prognosis evaluation of hematological malignancies (Drees and Pegtel, 2020;Gargiulo et al, 2020;Seimiya et al, 2020). However, until recently, there are still not abundant studies regarding the predictive role of exosomal miRNAs in DLBCL.…”

Section: Introductionmentioning

confidence: 91%

Circulating Exosomal MiR-107 Restrains Tumorigenesis in Diffuse Large B-Cell Lymphoma by Targeting 14-3-3η

Liu

Han

et al. 2021

Front. Cell Dev. Biol.

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Exosomes, nanometer-sized membranous vesicles in body fluids, have emerged as promising non-invasive biomarkers for cancer diagnosis. However, the function of exosomes in diffuse large B-cell lymphoma (DLBCL) remains elusive. This study aimed to investigate the role of exosomal miR-107 in lymphomagenesis and explore its clinical significance. In this study, decreased exosomal miR-107, miR-375-3p, and upregulated exosomal miR-485-3p were detected in the plasma of DLBCL patients and showed potential diagnostic value. Downregulated miR-107 expression was associated with advanced Ann Arbor stage, high IPI score, LDH, and β2-MG level in DLBCL patients. Overexpression of miR-107 by miR-107 Agomir significantly abrogated cell proliferation, induced apoptosis, and inhibited cell invasion in vitro, and repressed tumor growth in vivo. Moreover, the downregulation of miR-107 went in the opposite direction. The target genes of miR-107 were mainly enriched in the PI3K-Akt, Hippo, and AMPK signaling pathways. Notably, upregulated 14-3-3η (YWHAH) was suppressed by miR-107 in DLBCL, suggesting that miR-107 may restrain tumorigenesis by targeting 14-3-3η. In summary, this study unveils the function of miR-107 in lymphomagenesis, highlighting its potential as a diagnostic and prognostic indicator and as a new therapeutic target in the management of DLBCL.

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“…CircRNA are connected to the upstream shear acceptor site through the downstream splicing donor site, and reverse splicing is carried out to form a covalently closed continuous loop (Seimiya et al, 2020). CircRNAs in the cytoplasm of eukaryotic cells were observed using electron microscopy in 1979, and were subsequently found as a pathogenic RNA infection in higher plants (Hsu and Coca-Prados, 1979).…”

Section: Circrnasmentioning

confidence: 99%

Non-Coding RNAs Regulate Placental Trophoblast Function and Participate in Recurrent Abortion

et al. 2021

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Recurrent spontaneous abortion (RSA) is a serious pregnancy complication with an increasing clinical incidence. The various causes of recurrent abortion are complicated. Developments in genetics, immunology, and cell biology have identified important roles of non-coding RNAs (ncRNAs) in the occurrence and progress of recurrent abortion. NcRNAs can affect the growth, migration, and invasion of placental trophoblasts by regulating cell processes such as the cell cycle, apoptosis, and epithelial-mesenchymal transformation. Therefore, their abnormal expression might lead to the occurrence and development of RSA. NcRNAs include small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), ribosomal RNA (rRNA), transfer, RNA (tRNA), circular RNA (cRNA), and Piwi-interacting RNA (piRNA). In this review, we discuss recent research that focused on the function and mechanism of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNA (circRNA) in regulating placental trophoblasts. The use of ncRNAs as potential diagnostic and predictive biomarkers in RSA is also discussed to provide future research insights.

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Emerging Roles of Exosomal Circular RNAs in Cancer

Cited by 61 publications

References 80 publications

Circular RNA hsa_circ_0081343 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-210-5p/DLX3 axis

Circular RNA hsa_circ_0081343 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-210-5p/DLX3 axis

Circulating Exosomal MiR-107 Restrains Tumorigenesis in Diffuse Large B-Cell Lymphoma by Targeting 14-3-3η

Non-Coding RNAs Regulate Placental Trophoblast Function and Participate in Recurrent Abortion

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