microRNA arm-imbalance in part from complementary targets mediated decay promotes gastric cancer progression
microRNA arm-imbalance in part from complementary targets mediated decay promotes gastric cancer progression
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互补靶标介导的微小RNA臂不平衡促进胃癌进展
DOI：
10.1038/s41467-019-12292-5
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发表时间：
2019-09-27
影响因子：
16.6
通讯作者：
Yu, Jia
中科院分区：
文献类型：
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作者：
Zhang, Zhengyi;Pi, Jingnan;Yu, Jia
链选择是microRNA生物发生的最后一步，在这个过程中，功能成熟的miRNAs是由一条或两条前体臂产生的。在发育和组织形成过程中，链选择的偏好是多种多样的，但其病理作用尚不清楚。在这里，我们发现来自同一前体的两个miRNA臂miR-574-5p和miR-574-3p被反向表达，并在胃癌进展中发挥完全相反的作用。高-5p和低-3p表达模式与胃癌患者较高的TNM分期和不良预后显著相关。MiR-574-5p/-3p比值的升高，称为miR-574臂失衡，部分是由于它们在胃癌发生过程中高度互补靶点的动态表达，而miR-574的臂失衡又参与了胃癌的发生发展。我们的结果表明miR-574臂失衡促进了胃癌的进展，重新修饰miR-574靶分子的动态平衡可能是一种有希望的胃癌治疗策略。
Strand-selection is the final step of microRNA biogenesis in which functional mature miRNAs are generated from one or both arms of precursor. The preference of strand-selection is diverse during development and tissue formation, however, its pathological effect is still unknown. Here we find that two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, are inversely expressed and play exactly opposite roles in gastric cancer progression. Higher-5p with lower-3p expression pattern is significantly correlated with higher TNM stages and poor prognosis of gastric cancer patients. The increase of miR-574-5p/-3p ratio, named miR-574 arm-imbalance is partially due to the dynamic expression of their highly complementary targets in gastric carcinogenesis, moreover, the arm-imbalance of miR-574 is in turn involved and further promotes gastric cancer progression. Our results indicate that miR-574 arm-imbalance contribute to gastric cancer progression and re-modification of the miR-574-targets homeostasis may represent a promising strategy for gastric cancer therapy.