实用医学杂志 ›› 2021, Vol. 37 ›› Issue (2): 182-187.doi: 10.3969/j.issn.1006⁃5725.2021.02.011

• 基础研究 • 上一篇    下一篇

circ_NEK6靶向miR⁃370⁃3p对分化型甲状腺癌131I耐受细胞恶性生物学行为的影响

陈富坤, 邓智勇, 刘超,2吕娟, 贾莉,杨传周,刘鹏杰,冯志平   

  1. 1 云南省肿瘤医院核医学科(昆明650118);2 昆明医科大学第三附属医院核医学科(昆明650118)
  • 出版日期:2021-01-25 发布日期:2021-01-25
  • 通讯作者: 冯志平 E⁃mail:zpfeng19@126.com
  • 基金资助:
    云南省科技厅⁃昆明医科大学应用基础研究联合专项面上项目基金资助项目(编号:2019FE001(⁃247))

Effect of circ_NEK6 on malignant biological behavior of 131I⁃resistant differentiated thyroid carcinoma cells via targeting miR⁃370⁃3p

CHEN Fukun,DENG Zhiyong,LIU Chao,LÜ Juan,JIA Li,YANG Chuanzhou,LIU Pengjie,FENG Zhiping#br#   

  1. Department of Nuclear Medicine,Yunnan Cancer Hospital,Kunming 650118,China *Department of Nuclear Medicine,the Third Affiliated Hospital of Kunming Medical University,Kunming 650118,China

  • Online:2021-01-25 Published:2021-01-25
  • Contact: FENG Zhiping E⁃mail:zpfeng19@126.com

摘要:

目的 探讨 circ_NEK6 对分化型甲状腺癌(DTC)131I 耐受细胞恶性生物学行为的影响以及其 作用机制。方法 采用 RT⁃qPCR 检测 DTC 组织和细胞系中 circ_NEK6 miR⁃370⁃3p 的表达;采用 CCK⁃8 法、流式细胞术及 Transwell 法检测 131I 耐受 Res⁃BCPAP 细胞增殖、凋亡水平、侵袭和迁移能力;双荧光素酶 报告基因验证 circ_NEK6 miR⁃370⁃3p 的靶向关系。结果 circ_NEK6 131I 耐受 DTC 组织中的表达高于 131I 敏感组织,且其在 DTC 细胞中的表达高于人甲状腺滤泡上皮正常细胞,尤其是在 131I 耐受 Res⁃BCPAP 胞中的表达水平高于亲本 BCPAP 细胞。敲降 circ_NEK6 可抑制 Res⁃BCPAP 细胞增殖、侵袭和迁移能力,以 及诱导细胞凋亡。双荧光素酶报告实验表明,circ_NEK6 靶向负调控 miR⁃370⁃3p。敲降 circ_NEK6 靶向上 miR⁃370⁃3p 抑制 Res⁃BCPAP 细胞恶性生物学行为。结论 敲降 circ_NEK6 通过靶向 miR⁃370⁃3p 增强 DTC 细胞对131I放射敏感性,提示circ_NEK6可能是131I抵抗DTC 患者潜在的生物标志物和治疗靶点

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Abstract:

Objective To investigate the effect of circ_NEK6 on the malignant biological behavior of 131I⁃ resistant differentiated thyroid carcinoma (DTC)cells and its possible mechanism. Methods RT ⁃ qPCR was performed for the detection of circ_NEK6 and miR⁃370⁃3p in DTC tissues and cell lines. The proliferation,apoptosis migration and invasion abilities of Res⁃BCPAP cells was evaluated by CCK⁃8,flow cytometry,Transwell assay respectively. Dual⁃luciferase assay was conducted to prove the interaction of circ_NEK6 and miR⁃370⁃3p. Results circ_NEK6 was upregulated in the 131I⁃resistant DTC tissues compared with the 131I⁃sensitive DTC tissues,and its expression in DTC cell lines was higher than that in human thyroid follicular epithelial normal cells,especially in 131I⁃resistant Res⁃BCPAP cells was higher than that in parental BCPAP cells. Knockdown of circ_NEK6 decreased Res⁃BCPAP cell proliferation,migration and invasion,as well as promoted cell apoptosis. Besides,dual⁃luciferase reporter gene assay analysis results showed that circ_NEK6 could directly bind to and negatively regulate miR⁃370⁃ 3p expression. Functionally,circ_NEK6 suppression inhibited the malignant biological behavior of Res ⁃ BCPAP cells via targeting miR⁃370⁃3p. Conclusion Inhibition of circ_NEK6 enhanced the radio⁃sensitivity of 131I in DTC cells via targeting miR⁃370⁃3p,indicating that circ_NEK6 may act as a potential biomarker and therapeutic target for DTC patients with 131

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