microRNA-143 Protects Cells from DNA Damage-Induced Killing by Downregulating FHIT Expression
microRNA-143 Protects Cells from DNA Damage-Induced Killing by Downregulating FHIT Expression
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microRNA-143 通过下调 FHIT 表达来保护细胞免受 DNA 损伤诱导的杀伤
DOI：
10.1089/cbr.2010.0914
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发表时间：
2011-06-01
影响因子：
3.4
通讯作者：
Hu, Bao-cheng
中科院分区：
文献类型：
--
作者：
Lin, Yu-xiang;Yu, Fang;Hu, Bao-cheng
MicroRNAs(MiRNAs)是基因表达的转录后调节因子，在许多发育过程中发挥重要作用。最近的研究表明miRNAs在癌症发生中的作用。脆性组氨酸三联体(FHIT)基因缺失、甲基化和FHIT蛋白表达降低发生在约70%的人类上皮性肿瘤中，并与肿瘤的进展明显相关。尽管已有报道表明FHIT(-/-)细胞对包括电离辐射在内的多种DNA损伤诱导剂表现出更强的抵抗力，但针对FHIT的miRNAs在DNA损伤反应中如何发挥作用尚不清楚。本研究报告miR-143直接靶向FHIT，miR-143的过表达导致显著的G2期停滞，并保护细胞免受DNA损伤诱导的杀伤。这些结果表明，FHIT基因失活与DNA损伤后存活率的增加有关，也为基于miRNA的药物开发提供了两个方向的有用信息：保护细胞免受DNA损伤诱导的杀伤和增强细胞对放射治疗的敏感性。
MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression and play an important role in many developmental processes. Recent studies suggest roles of miRNAs in carcinogenesis. Fragile histidine triad (FHIT) gene deletion, methylation, and reduced Fhit protein expression occur in about 70% of human epithelial tumors and are clearly associated with tumor progression. Although it has been previously reported that Fhit(-/-) cells exhibit more resistance to multi-DNA damage inducers, including ionizing radiation, it remains unclear how miRNAs targeting FHIT in DNA damage response play the role. This study reports that miR-143 directly targets FHIT and that overexpression of miR-143 results in significant G2-phase arrest and protects cells from DNA damage-induced killing. These results indicate an association of FHIT gene inactivation with increased survival after DNA damage and also provide useful information for miRNA-based drug development in two directions: protect cells from DNA damage-induced killing and sensitize cells to radiation therapy.