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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis

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          Abstract

          Background

          Circular RNAs (circRNAs) have been reported to be involved in regulating the development of breast cancer. Paclitaxel (PTX) can be used for the chemotherapy of breast cancer. The study aimed to explore the role and mechanism of circ_0006528 in PTX-resistant breast cancer progression.

          Methods

          The levels of circ_0006528, microRNA-1299 (miR-1299) and cyclin-dependent kinase 8 ( CDK8) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to confirm that the circ_0006528 was a circular RNA. PTX resistance and cell proliferation were determined by Cell counting kit-8 (CCK-8) assay. Cell apoptosis, migration and invasion were analyzed by flow cytometry and Transwell assays, respectively. The levels of all proteins were examined by Western blot. The interaction between circ_0006528 and miR-1299 or CDK8 was predicted by online database confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft mice model was constructed to reveal the role of circ_0006528 on tumor growth in vivo.

          Results

          Circ_0006528 was significantly up-regulated and miR-1299 was down-regulated in PTX-resistant breast cancer tissues and cells compared with control groups. CDK8 protein expression was dramatically upregulated in PTX-resistant breast cancer tissues and cells as compared to control groups. Loss-of-function experiments revealed that circ_0006528 knockdown decreased IC50 value of PTX and restrained proliferation, migration, invasion and autophagy, whereas induced apoptosis of PTX-resistant breast cancer cells in vitro. The inhibitory effects of sh-circ_0006528 on the progression of PTX-resistant breast cancer cells were reversed by decreasing miR-1299 or increasing CDK8 expression. Furthermore, circ_0006528 could modulate CDK8 expression by sponging miR-1299. Circ_0006528 silencing impeded the growth of PTX-resistant tumors by regulating miR-1299/ CDK8 axis in vivo.

          Conclusion

          Circ_0006528 partially contributed to PTX resistance of breast cancer cells through up-regulating CDK8 expression by sponging miR-1299.

          Most cited references20

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          Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment.

          Heather Greenlee, Melissa DuPont-Reyes, Lynda G Balneaves … (2017)
          Answer questions and earn CME/CNE Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232. © 2017 American Cancer Society.
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            NUDT21 regulates circRNA cyclization and ceRNA crosstalk in hepatocellular carcinoma

            Xiaojing Li, Junyao Ding, Xueying Wang … (2019)
            Circular RNAs (circRNAs) are a novel class of RNAs, which involve in many physiological processes and participate in many diseases, especially in cancer. Previous reports showed circRNAs were globally downregulated in hepatocellular carcinoma (HCC) and a lot of circRNAs involved in the tumorigenesis and metastasis of HCC. To understand the underlying mechanism of circRNAs' reduction, we explored the relationship between circRNA biogenesis and NUDT21, which was a RNA splice factor downregulated in HCC, and we found that NUDT21 elevated the formation of circRNA, and the UGUA sequences were critical for the cyclization of circRNA. Knockdown of NUDT21 disrupted the competitive endogenous RNA (ceRNA) pathway of circRNA-miRNA-mRNA, and overexpression of the downregulated circRNA could assist the NUDT21-mediated tumor suppression in HCC cells. In conclusion, the loss of NUDT21 prevented the cyclization of circRNA in HCC; without circRNA absorption, miRNAs were released to suppress the tumor-suppressor genes, leading to the uncontrolled cell proliferation.
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              hsa_circRNA_0006528 as a competing endogenous RNA promotes human breast cancer progression by sponging miR-7-5p and activating the MAPK/ERK signaling pathway

              Danfeng Gao, Xiaowei Qi, Xiufen Zhang … (2019)
              Emerging research has indicated that circular RNAs (circRNAs), a novel class of non-coding RNAs, play a vital role in human tumorigenesis and progression. Our previous results suggested that hsa_circ_0006528 (circ_0006528), a circRNA with an unknown function, mediates adriamycin resistance in human breast cancer cells. However, the role of circ_0006528 in breast cancer progression remains unknown. Here, we investigated the probable involvement of circ_0006528 in breast cancer. We analyzed a cohort of 97 patients and found that circ_0006528 expression was significantly upregulated in human breast cancer tissues compared with that in adjacent non-tumorous tissues and was significantly associated with advanced tumor-node-metastasis (TNM) stage and poor prognosis. In addition, we found that in breast cancer cells, circ_0006528 could promote DNA synthesis and cell proliferation, invasion, and migration. Downregulating circ_0006528 induced G2 phase arrest and cell apoptosis. Further mechanistic studies revealed that circ_0006528 could sponge endogenous miR-7-5p and inhibit its activity. We also identified Raf1, which activates the MAPK/ERK signaling pathway, as a target of miR-7-5p and determined that circ_0006528 promotes breast cancer growth, invasion, and migration by promoting the expression of Raf1 and activates the MAPK/ERK pathway. Thus, this study provides the first evidence of the circ_0006528/miR-7-5p/Raf1/MEK/ERK regulatory network in the development of breast cancer and suggests that circ_0006528 is a potential therapeutic target and prognostic predictor for breast cancer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (publisher-id): ott
                Journal ID (pmc): ott
                Title: OncoTargets and therapy
                Publisher: Dove
                ISSN (Electronic): 1178-6930
                Publication date (Electronic): 24 September 2020
                Publication date Collection: 2020
                Volume: 13
                Pages: 9497-9511
                Affiliations
                [1 ]Department of Integrated Traditional Chinese and Western Medicine in Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University , Luoyang, People’s Republic of China
                [2 ]Department of Oncology and Hematology, No. 989 Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army , Pingdingshan, People’s Republic of China
                Author notes
                Correspondence: Huifeng Shui Department of Integrated Traditional Chinese and Western Medicine in Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University , No. 288 Zhongzhou Middle Road, Luoyang471009, Henan, People’s Republic of ChinaTel +86-379-63892209 Email dskvmf@163.com
                Article
                Publisher ID: 252886
                DOI: 10.2147/OTT.S252886
                PMC ID: 7522311
                PubMed ID: 33061434
                SO-VID: 95f8b403-3cf3-46ab-ba89-350258d6928d
                Copyright © © 2020 Liu 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 : 07 March 2020
                Date accepted : 07 August 2020
                Page count
                Figures: 9, References: 32, Pages: 15
                Funding
                No funding was received.
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: breast cancer,paclitaxel resistance,circ_0006528,mir-1299,cdk8
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: breast cancer, paclitaxel resistance, circ_0006528, mir-1299, cdk8

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