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MiR-1587 Regulates DNA Damage Repair and the Radiosensitivity of CRC Cells via Targeting LIG4.
Dose-Response ( IF 2.3 ) Pub Date : 2020-06-24 , DOI: 10.1177/1559325820936906
Ruixue Liu 1, 2 , Liping Shen 2 , Chuxian Lin 2 , Junyan He 2 , Qi Wang 2 , Zhenhua Qi 2 , Qingtong Zhang 3 , Meijuan Zhou 1 , Zhidong Wang 2
Affiliation  

DNA is subject to a range of endogenous and exogenous insults that can impair DNA replication and lead to DNA double-strand breaks (DSBs). The repair capacity of cancer cells mediates their radiosensitivity, but the roles of miR-1587 during radiation resistance are poorly characterized. In this study, we explored whether miR-1587 regulates the growth and radiosensitivity of colorectal cancer (CRC) cells through its ability to regulate DNA Ligase4 (LIG4). We found that CRC cells in which miR-1587 was overexpressed inhibited cell growth and promoted apoptosis through increasing DSBs and promoting cell cycle arrest. We found that overexpression of miR-1587 significantly inhibited LIG4 messenger RNA and protein expression and further revealed the ability of miR-1587 to directly bind to the LIG4-3′-untranslated region through dual-luciferase reporter assays. More notably, miR-1587 mimics increased the radiosensitivity of CRC cells. Taken together, we show that miR-1587 overexpression enhances the formation of DSBs, arrests CRC cell growth, and enhances the radiosensivity of CRC cells through the direct repression of LIG4 expression. These results reveal novel roles for miR-1587 during DNA damage repair and the radiosensivity of CRC cells. This highlights miR-1587 as a novel therapeutic target for CRC.



中文翻译:

MiR-1587通过靶向LIG4调节DNA损伤修复和CRC细胞的放射敏感性。

DNA受到一系列内源性和外源性损伤,可能会损害DNA复制并导致DNA双链断裂(DSB)。癌细胞的修复能力介导了它们的放射敏感性,但是miR-1587在抗辐射过程中的作用尚不明确。在这项研究中,我们探讨了miR-1587是否通过调节DNA Ligase4(LIG4)的能力来调节结直肠癌(CRC)细胞的生长和放射敏感性。我们发现其中miR-1587过表达的CRC细胞通过增加DSB和促进细胞周期停滞来抑制细胞生长并促进细胞凋亡。我们发现,miR-1587的过表达显着抑制了LIG4信使RNA和蛋白质的表达,并进一步揭示了miR-1587通过双荧光素酶报告基因检测法直接与LIG4-3'-非翻译区结合的能力。更值得注意的是,miR-1587模拟物增加了CRC细胞的放射敏感性。综上所述,我们显示miR-1587过表达增强了DSB的形成,阻止了CRC细胞的生长,并通过直接抑制LIG4表达增强了CRC细胞的放射敏感性。这些结果揭示了miR-1587在DNA损伤修复和CRC细胞的放射敏感性中的新作用。这突显了miR-1587作为CRC的新型治疗靶标。我们显示miR-1587过表达增强了DSB的形成,阻止了CRC细胞的生长,并通过直接抑制LIG4的表达增强了CRC细胞的放射敏感性。这些结果揭示了miR-1587在DNA损伤修复和CRC细胞的放射敏感性中的新作用。这突显了miR-1587作为CRC的新型治疗靶标。我们显示miR-1587过表达增强了DSB的形成,阻止了CRC细胞的生长,并通过直接抑制LIG4的表达增强了CRC细胞的放射敏感性。这些结果揭示了miR-1587在DNA损伤修复和CRC细胞的放射敏感性中的新作用。这突显了miR-1587作为CRC的新型治疗靶标。

更新日期:2020-06-30
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