Circ_0055625 敲低通过调控 miR-338-3p/MSI1 轴抑制结肠癌的肿瘤发生和提高放射敏感性。
Circ_0055625 knockdown inhibits tumorigenesis and improves radiosensitivity by regulating miR-338-3p/MSI1 axis in colon cancer.
机构信息
Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Physiology, Hebei Medical University, Shijiazhuang, 050011, Hebei Province, China.
出版信息
World J Surg Oncol. 2021 Apr 21;19(1):131. doi: 10.1186/s12957-021-02234-1.
BACKGROUND
Radiotherapy is a main therapeutic method for cancers, including colon cancer. In the current study, we aim to explore the effects of circular RNA (circRNA) circ_0055625 in the progression and radiosensitivity of colon cancer and the underlying mechanism.
METHODS
The expression of circ_0055625 and musashi homolog 1 (MSI1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). MSI1 protein expression was determined by Western blot. Cell proliferation was assessed by cell counting kit-8 (CCK-8) and colony formation assays. Cell survival fraction, apoptosis, and invasion were investigated by colony formation assay, flow cytometry analysis, and transwell invasion assay, respectively. Cell migration was detected by wound-healing and transwell migration assays. The binding relationship between microRNA-338-3p (miR-338-3p) and circ_0055625 or MSI1 was predicted by online databases and identified by Dual-Luciferase Reporter Assay. The effects of circ_0055625 silencing on the tumor formation and radiosensitivity of colon cancer in vivo were explored by in vivo tumor formation assay.
RESULTS
Circ_0055625 and MSI1 were upregulated in colon cancer tissues and cells relative to control groups. Radiation treatment apparently increased the expression of circ_0055625 and MSI1 in colon cancer cells. Circ_0055625 knockdown or MSI1 silencing repressed cell proliferation, migration, and invasion and promoted cell apoptosis and radiosensitivity in colon cancer. Also, circ_0055625 silencing-mediated effects were attenuated by MSI1 overexpression. Additionally, circ_0055625 silencing reduced MSI1 expression, which could be attenuated by miR-338-3p inhibitor. Mechanically, circ_0055625 acted as a sponge for miR-338-3p to regulate MSI1. Furthermore, circ_0055625 knockdown hindered tumor growth and improved radiosensitivity in vivo.
CONCLUSION
Circ_0055625 repression inhibited the progression and radioresistance of colon cancer by downregulating MSI1 through sponging miR-338-3p. This result might provide a theoretical basis for improving the therapy of colon cancer with radiation.
背景
放射治疗是癌症的主要治疗方法，包括结肠癌。在本研究中，我们旨在探讨环状 RNA (circRNA) circ_0055625 在结肠癌进展和放射敏感性中的作用及其潜在机制。
方法
采用实时定量聚合酶链反应 (qRT-PCR) 检测 circ_0055625 和 Musashi 同源物 1 (MSI1) mRNA 的表达。采用 Western blot 检测 MSI1 蛋白表达。用细胞计数试剂盒-8 (CCK-8) 和集落形成实验评估细胞增殖。通过集落形成实验、流式细胞术分析和 Transwell 侵袭实验分别检测细胞存活分数、细胞凋亡和侵袭。用划痕愈合和 Transwell 迁移实验检测细胞迁移。通过在线数据库预测 microRNA-338-3p (miR-338-3p) 与 circ_0055625 或 MSI1 的结合关系，并通过双荧光素酶报告基因实验进行验证。通过体内肿瘤形成实验探讨 circ_0055625 沉默对体内结肠癌肿瘤形成和放射敏感性的影响。
结果
circ_0055625 和 MSI1 在结肠癌组织和细胞中上调，与对照组相比。放射治疗明显增加了结肠癌细胞中 circ_0055625 和 MSI1 的表达。circ_0055625 敲低或 MSI1 沉默抑制了结肠癌的增殖、迁移和侵袭，促进了细胞凋亡和放射敏感性。此外，MSI1 的过表达减弱了 circ_0055625 沉默介导的作用。此外，circ_0055625 沉默降低了 MSI1 的表达，而 miR-338-3p 抑制剂可以减弱这种作用。机制上，circ_0055625 作为 miR-338-3p 的海绵来调节 MSI1。此外，circ_0055625 敲低抑制了体内肿瘤生长并提高了放射敏感性。
结论
circ_0055625 抑制通过海绵吸附 miR-338-3p 下调 MSI1 抑制结肠癌的进展和放射抵抗。这一结果可能为提高结肠癌放射治疗的疗效提供理论依据。
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