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      Circular RNA circ-BNC2 (hsa_circ_0008732) inhibits the progression of ovarian cancer through microRNA-223-3p/ FBXW7 axis

      research-article
      , ,
      Journal of Ovarian Research
      BioMed Central
      Ovarian cancer, circ-BNC2, miR-223-3p, FBXW7, Proliferation

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          Abstract

          Background

          Circular RNAs (circRNAs) are reported to be key regulators in the progression of human cancers. This work focuses on the function and molecular mechanism of circRNA-BNC2 (circ-BNC2) (also known as hsa_circ_0008732) in ovarian cancer (OC).

          Methods

          Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect circ-BNC2, microRNA-223-3p (miR-223-3p) and F-box and WD repeat domain containing 7 (FBXW7) mRNA expressions in OC tissues and cells. Besides, cell counting kit 8 (CCK-8), transwell assay and cell cycle assays were executed to assess the proliferative, migrative, invasive abilities, and cell cycle progression of OC cells, respectively. Dual-luciferase reporter gene assay and RNA pull-down assay were used to validate the targeting relationships between miR-223-3p and circ-BNC2 or FBXW7. Western blot was adopted to determine FBXW7 protein levels in OC cells.

          Results

          Circ-BNC2 expression was downregulated in OC tissues and cell lines, which was associated with higher FIGO stage and lymph node metastasis of OC patients. Circ-BNC2 overexpression repressed the proliferation, migration, invasion of OC cells and induced cell cycle arrest, while silencing circ-BNC2 worked oppositely. Mechanistically, circ-BNC2 could upregulate FBXW7 expression in OC cells via sponging miR-223-3p.

          Conclusion

          Circ-BNC2 suppresses the progression of OC via regulating miR-223-3p / FBXW7 axis. Our findings provided potential biomarker for OC therapy.

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          Most cited references29

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          Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway

          Background CircRNA has emerged as a new non-coding RNA that plays crucial roles in tumour initiation and development. ‘MiRNA sponge’ is the most reported role played by circRNAs in many tumours. The AKT/mTOR axis is a classic signalling pathway in cancers that sustains energy homeostasis through energy production activities, such as the Warburg effect, and blocks catabolic activities, such as autophagy. Additionally, the AKT/mTOR axis exerts a positive effect on EMT, which promotes tumour metastasis. Methods We detected higher circNRIP1 expression in gastric cancer by performing RNA-seq analysis. We verified the tumour promotor role of circNRIP1 in gastric cancer cells through a series of biological function assays. We then used a pull-down assay and dual-luciferase reporter assay to identify the downstream miR-149-5p of circNRIP1. Western blot analysis and immunofluorescence assays were performed to demonstrate that the circNRIP1-miR-149-5p-AKT1/mTOR axis is responsible for the altered metabolism in GC cells and promotes GC development. We then adopted a co-culture system to trace circNRIP1 transmission via exosomal communication and RIP experiments to determine that quaking regulates circNRIP1 expression. Finally, we confirmed the tumour suppressor role of microRNA-133a-3p in vivo in PDX mouse models. Results We discovered that knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in GC cells. MiR-149-5p inhibition phenocopied the overexpression of circNRIP1 in GC cells, and overexpression of miR-149-5p blocked the malignant behaviours of circNRIP1. Moreover, it was proven that circNRIP1 can be transmitted by exosomal communication between GC cells, and exosomal circNRIP1 promoted tumour metastasis in vivo. We also demonstrated that quaking can promote circNRIP1 transcription. In the final step, the tumour promotor role of circNRIP1 was verified in PDX models. Conclusions We proved that circNRIP1 sponges miR-149-5p to affect the expression level of AKT1 and eventually acts as a tumour promotor in GC. Electronic supplementary material The online version of this article (10.1186/s12943-018-0935-5) contains supplementary material, which is available to authorized users.
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            Circular RNA hsa_circ_001783 regulates breast cancer progression via sponging miR-200c-3p

            Increasing evidence suggests circular RNAs (circRNAs) exert critical functions in tumor progression via sponging miRNAs (microRNAs). However, the role of circRNAs in breast cancer remains unclear. Here we systematically analyzed the circular RNAs in breast cancer based on their characteristic in sponging disease-specific miRNAs and identified hsa_circ_001783 as a top ranked circRNA in our computation and verified its high expression in both breast cancer cells and cancer tissue. A higher level of hsa_circ_001783 was significantly correlated with heavier tumor burden and poorer prognosis of patients with breast cancer. Knockdown of this circRNA remarkably inhibited the proliferation and invasion of breast cancer cells. Importantly, hsa_circ_001783 promoted progression of breast cancer cells via sponging miR-200c-3p. Taken together, hsa_circ_001783 may serve as a novel prognostic and therapeutic target for breast cancer.
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              CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression

              Circular RNA (circRNA) is shown to participate in various tumors, including lung cancer. Although a few circRNAs involved in lung cancer are reported, whether circRNA negatively regulates lung cancer development remains elusive. In this study, we showed hsa_circ_100395 expression was decreased in lung cancer tissues. Besides, hsa_circ_100395 level was inversely correlated with TNM stage and metastases in lung cancer and low hsa_circ_100395 expression in patients predicted poor prognosis. Overexpression of hsa_circ_100395 dramatically inhibited lung cancer cell proliferation, arrested cell-cycle progression and reduced cell migration and invasion in vitro . Xenograft experiments showed that hsa_circ_100395 overexpression delayed tumor growth in vivo . Mechanistically, we showed hsa_circ_100395 serves as a sponge for miR-1228 targeting TCF21 in lung cancer. Rescue assays indicated that hsa_circ_100395 regulates lung cancer cell proliferation, migration and invasion through modulating miR-1228/TCF21 pathway. Altogether, our study reveals a novel regulatory loop that hsa_circ_100395/miR-1228/TCF21 axis modulates lung cancer development. Abbreviations : circRNA: circular RNA; miRNA: microRNA; RNA-FISH: RNA fluorescence in situy bridization; qRT-PCR: Reverse transcription and quantitative real-time PCR.
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                Author and article information

                Contributors
                ivki36994@163.com
                229158546@qq.com
                929409442@qq.com
                Journal
                J Ovarian Res
                J Ovarian Res
                Journal of Ovarian Research
                BioMed Central (London )
                1757-2215
                14 August 2022
                14 August 2022
                2022
                : 15
                : 95
                Affiliations
                GRID grid.413390.c, ISNI 0000 0004 1757 6938, Department of Gynaecology, , Affiliated Hospital of Zunyi Medical University, ; Dalian Road No.149, Huichuan District, 563000 Zunyi, Guizhou Province China
                Author information
                http://orcid.org/0000-0002-7408-6025
                Article
                1025
                10.1186/s13048-022-01025-w
                9377053
                35965327
                a13c4dc9-f586-410f-8bad-00cd17421615
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 10 September 2021
                : 29 July 2022
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Obstetrics & Gynecology
                ovarian cancer,circ-bnc2,mir-223-3p,fbxw7,proliferation
                Obstetrics & Gynecology
                ovarian cancer, circ-bnc2, mir-223-3p, fbxw7, proliferation

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