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  • Midostaurin sues n br C Positive correlation

    2022-09-07

    sues (n = 248).
    (C) Positive correlation between circMTO1 and S100A1 levels were analyzed in cervical cancer patients using the Pearson’s
    correlation coefficient analysis.
    (D) Negative correlation between miR-6893 and S100A1 levels were analyzed in cervical cancer patients using the Pearson’s correlation coefficient analysis.
    Fig. 8. Schematic diagram shows the mechanism by which circMTO1 con-tributes to cervical cancer tumorigenesis and chemoresistance.
    Conflict of interest
    We declare no conflict of interest.
    Acknowledgement
    We thank Zhongping Cheng for helpful discussions and critical reading. 
    Appendix A. Supplementary data
    References
    Contents lists available at ScienceDirect
    Cancer Letters
    journal homepage: www.elsevier.com/locate/canlet
    Original Articles
    CircNR3C1 inhibits proliferation of Midostaurin cancer cells by sponging miR- T 27a-3p and downregulating cyclin D1 expression
    Fuxin Zheng a,b,1, Miao Wanga,1, Yawei Lic,1, Chao Huanga, Dan Taod, Fei Xiea, Hui Zhanga, Jiayin Suna, Chuanhua Zhangb, Chaohui Gue , Zhendi Wanga,∗∗, Guosong Jianga,∗ a Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China b Department of Urology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China c Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, China d Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, 430050, China e Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
    Keywords:
    Bladder cancer
    CircNR3C1
    Cyclin D1
    Accumulating evidences suggest that circular RNAs play vital roles in human cancers. Previously, we found that circHIPK3 suppressed invasion of bladder cancer cells via sponging miR-558 and downregulating heparanase expression. In this study, we discovered that a circular RNA derived from NR3C1 (circNR3C1) was down-regulated in bladder cancer tissues and cell lines according to RNA-Seq data and qRT-PCR analysis. Functionally, we found that overexpression of circNR3C1 could significantly inhibit Midostaurin cell cycle progression and proliferation of bladder cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistically, we demonstrated that circNR3C1 possessed four targeting sites of miR-27a-3p and could effectively sponge miR-27a-3p to suppress the expression of cyclin D1. Furthermore, we revealed that miR-27a-3p functioned as an oncogene through inter-acting with 5′UTR of cyclin D1 to enhance its expression, which led to promote cell cycle progression and proliferation in bladder cancer cells. Conclusively, our findings further confirm the hypothesis that circRNAs function as “microRNA sponges”, and our data suggest that circNR3C1 and miR-27a-3p would be potential therapeutic targets for bladder cancer treatment.
    1. Introduction
    Bladder cancer is one of the most frequently occurring malignancies of urinary system worldwide [1]. Both the incidence and mortality of bladder cancer have risen steadily in recent decades. Recent studies suggest that bladder cancer comprises a group of molecularly hetero-geneous diseases which lead to various clinical features and possess diverse therapeutic responses [2]. Thus, development of precise stra-tegies is worthy and important.
    As a new type of RNAs, covalently closed circular RNA molecules (circRNAs) were originally discovered in plant viroids [3], hepatitis virus [4] and eukaryotic cells [5] more than 40 years ago. Subse-quently, a handful circular RNAs were identified in human [6,7] and mouse [8], and were considered as by-products of aberrant splicing with little functional potential [9]. Next-generation RNA sequencing (RNA-Seq) from nonpolyadenylated RNA transcripts and bioinformatic