LncRNA OIP5-AS1 regulates radioresistance by targeting DYRK1A through miR-369-3p in colorectal cancer cells

LncRNA OIP5-AS1 regulates radioresistance by targeting DYRK1A through miR-369-3p in colorectal cancer cells
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LncRNA OIP5-AS1 通过 miR-369-3p 靶向 DYRK1A 调节结直肠癌细胞的放射抗性

DOI:
10.1016/j.ejcb.2018.04.005
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发表时间:
2018-06-01
影响因子:
6.6
通讯作者:
Xiong, Hua
Xiong, Hua
中科院分区:
生物学3区
文献类型:
--
作者:
Zou, Yanmei;Yao, Shuo;Xiong, Hua

文献摘要

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目的探讨lncRNA OIP 5-AS 1在大肠癌细胞辐射抗性中的作用。通过qRT-PCR测量CRC细胞系中OIP 5-AS 1、miR-369- 3 p和DYRK 1A的表达水平。Western blot检测DYRKIA蛋白表达。通过双荧光素酶报告基因分析验证OIP 5-AS 1、miR-369- 3 p和DYRKIA之间的靶向关系。采用MTT法、克隆形成存活法和流式细胞术检测OIP 5-AS 1和DYRK 1A对大肠癌细胞活性和凋亡的影响,分析OIP 5-AS 1和DYRK 1A对大肠癌细胞辐射抗性的影响。OIP 5-AS 1抑制miR-369- 3 p的表达,从而上调miR-369- 3 p下游基因DYRKIA的表达。结论:LncRNA OIP 5-AS 1通过miR-369- 3 p调控DYRKIA的表达,抑制细胞活力,促进辐射诱导的细胞凋亡,增强辐射敏感性。
Object This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells.Methods: Microarray analysis was used to screen out IncRNAs differentially expressed in radio-resistant CRC cell lines. Expression levels of OIP5-AS1, miR-369-3p and DYRKIA in CRC cell lines were measured by qRT-PCR. Protein expression of DYRKIA was determined by western blot. The target relationships among OIP5-AS1, miR-369-3p and DYRKIA were validated by dual luciferase reporter assay. Impacts of OIP5-AS1 or DYRKIA on CRC cellular activity and apoptosis were investigated by MIT assay, clonogenic survival assay and flow cytometry to analyze OIP5-AS1 or DYRK1A's effect on radioresistance of CRC cells.Results: LncRNA OIP5-AS1 and DYRKIA were down-regulated in radio-resistant CRC cell lines. OIP5-AS1 suppressed the expression of miR-369-3p, thus up-regulating DYRKIA, the downstream gene of miR-369-3p. OIP5AS1 and DYRKIA impaired cell clonogenic survival and promoted cell apoptosis after irradiation, improving radiosensitivity of CRC cells.Conclusion: LncRNA OIP5-AS1 suppressed cell viability, promoted radio-induced apoptosis, and enhanced the radiosensitivity of CRC cells by regulating DYRKIA expression through miR-369-3p.