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      CircRNA Circ_0001721 Promotes the Progression of Osteosarcoma Through miR-372-3p/MAPK7 Axis

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          Abstract

          Background

          Osteosarcoma (OS) is the most common bone tumor. Many studies have reported that circular RNAs (circRNAs) play an important role in the development of a variety of human cancers. However, the underlying mechanism of circ_0001721 in regulating osteosarcoma progression remains unknown.

          Materials and Methods

          Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001721, miR-372-3p, and mitogen-activated protein kinase 7 (MAPK7) in osteosarcoma tissues and cells. Besides, glycolysis was investigated by glucose consumption, lactate production and hexokinase II (HK2) protein level. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry, separately. Cell migration and invasion were determined by transwell assay. Moreover, the protein levels of HK2 and epithelial-to-mesenchymal transition (EMT) markers were determined by Western blot analysis. The relationship between miR-372-3p and circ_0001721 or MAPK7 was predicated by starbase v3.0 and confirmed by dual-luciferase reporter assay or RNA binding protein immunoprecipitation (RIP) assay. Murine xenograft model was established to investigate the role of circ_0001721 in vivo.

          Results

          The levels of circ_0001721 and MAPK7 were upregulated in osteosarcoma tissues and cells, while miR-372-3p was downregulated. Knockdown of circ_0001721 inhibited glycolysis, cell proliferation, cell migration, invasion and epithelial-to-mesenchymal transition (EMT), and promoted apoptosis. Circ_0001721 was validated as a sponge of miR-372-3p and mediated glycolysis, cell proliferation, apoptosis, migration, invasion, and EMT of osteosarcoma cells through miR-372-3p. MAPK7 was a target of miR-372-3p and overexpression of MAPK7 attenuated anti-cancer role of miR-372-3p in OS cells. Further studies revealed that circ_0001721 regulates MAPK7 expression via sponging miR-372-3-p. Finally, knockdown of circ_0001721 inhibited tumor progression in vivo.

          Conclusion

          Circ_0001721 promoted osteosarcoma development through the miR-372-3p/MAPK7 axis.

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          Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression

          Yizheng Wu, Ziang Xie, Junxin Chen … (2019)
          Background As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. However, little is known about the role of circTADA2A, also named hsa_circ_0043278, in osteosarcoma (OS). Methods CircTADA2A was selected from a previously reported circRNA microarray comparing OS cell lines and normal bone cells. QRT-PCR was used to detect the expression of circTADA2A in OS tissue and cell lines. Luciferase reporter, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to confirm the binding of circTADA2A with miR-203a-3p. OS cells were stably transfected with lentiviruses, and Transwell migration, Matrigel invasion, colony formation, proliferation, apoptosis, Western blotting, and in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circTADA2A, miR-203a-3p and CREB3. Results Our findings demonstrated that circTADA2A was highly expressed in both OS tissue and cell lines, and circTADA2A inhibition attenuated the migration, invasion and proliferation of OS cells in vitro as well as tumorigenesis and metastasis in vivo. A mechanistic study revealed that circTADA2A could readily sponge miR-203a-3p to upregulate the expression of CREB3, which was identified as a driver gene in OS. Furthermore, miR-203a-3p inhibition or CREB3 overexpression could reverse the circTADA2A silencing-induced impairment of malignant tumor behavior. Conclusions CircTADA2A functions as a tumor promoter in OS to increase malignant tumor behavior through the miR-203a-3p/CREB3 axis, which could be a novel target for OS therapy. Electronic supplementary material The online version of this article (10.1186/s12943-019-1007-1) contains supplementary material, which is available to authorized users.
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            Pathogenic role of exosomes and microRNAs in HPV‐mediated inflammation and cervical cancer: A review

            Javid Sadri Nahand, Mohsen Moghoofei, Arash Salmaninejad … (2019)
            Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well-controlled, however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of non-coding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.
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              Reduction of circular RNA Foxo3 promotes prostate cancer progression and chemoresistance to docetaxel

              Zhiyuan Shen, Le Zhou, Chao Zhang … (2019)
              Dysregulation of circular RNA Foxo3 (circFoxo3) has been reported to be involved in breast cancer and non-small lung cancer progression. However, little is known about the role of circFoxo3 in prostate cancer, which the present study seeks to investigate. CircFoxo3 expression was analyzed in 22 low-grade prostate cancer samples, 24 high-graded prostate cancer samples, and 18 normal prostate tissues, finding that its quantity was significantly decreased in high-graded compared to low-grade prostate cancer and normal prostate tissues. CircFoxo3 inhibited prostate cancer cell survival, migration, invasion and chemoresistance to docetaxel, which was related to circFoxo3's repression of Foxo3 and EMT. Silencing circFoxo3 expression promoted prostate cancer cell survival, migration, invasion and chemoresistance to docetaxel, as well as the positive effects of androgen on prostate cancer viability. Delivery of circfoxo3 enhanced chemosensitivity to docetaxel of prostate tumor-bearing mice and prolonged the life span of mice, while reduction with siRNAs promoted chemoresistance to docetaxel and shorted the life span of the tumor-bearing mice. Targeting circFoxo3/Foxo3/EMT may provide an applicable strategy for exploring potential prognostic and therapeutic approaches for prostate cancer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Manag Res
                Journal ID (iso-abbrev): Cancer Manag Res
                Journal ID (publisher-id): cmar
                Journal ID (pmc): cancmanres
                Title: Cancer Management and Research
                Publisher: Dove
                ISSN (Electronic): 1179-1322
                Publication date (Electronic): 11 September 2020
                Publication date Collection: 2020
                Volume: 12
                Pages: 8287-8302
                Affiliations
                [1 ]Department of Orthopaedics, The Second Hospital of Shanxi Medical University , Taiyuan, People’s Republic of China
                [2 ]Department of Pathology, Tumor Hospital of Shanxi , Taiyuan, People’s Republic of China
                [3 ]Department of VitreoretinalSurgery, Shanxi Eye Hospital , Taiyuan, People’s Republic of China
                [4 ]Department of Digestive Minimally Invasive Surgery, Tumor Hospital of Shanxi , Taiyuan, People’s Republic of China
                [5 ]Comprehensive Examination Department, Children’s Hospital of Shanxi Province , Taiyuan, People’s Republic of China
                [6 ]Department of Urology Surgery, Shanxi Bethune Hospital , Taiyuan, People’s Republic of China
                [7 ]Department of Cardiology, Taiyuan Iron and Steel Group General Hospital , Taiyuan, People’s Republic of China
                [8 ]Department of Nephrology, Children’s Hospital of Shanxi Province , Taiyuan, People’s Republic of China
                [9 ]Department of Rehabilitation, Shanxi Huajin Orthopedic Hospital , Taiyuan, People’s Republic of China
                Author notes
                Correspondence: Junjun Shi Tel/fax +86 0351 6125623 Email gypfly147852@163.com
                Yunpeng Wen Tel/fax +86 0351 6185361 Email nmepvb@163.com
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: 244527
                DOI: 10.2147/CMAR.S244527
                PMC ID: 7498501
                PubMed ID: 32982424
                SO-VID: f9e86c71-f667-47fc-be06-74b8c8bb2efa
                Copyright © © 2020 Gao et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 02 January 2020
                Date accepted : 06 August 2020
                Page count
                Figures: 11, Tables: 2, References: 32, Pages: 16
                Funding
                There is no funding to report.
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: circ_0001721,mir-372-3p,mapk7,osteosarcoma
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: circ_0001721, mir-372-3p, mapk7, osteosarcoma

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