microRNA arm-imbalance in part from complementary targets mediated decay promotes gastric cancer progression

microRNA 臂不平衡部分源于互补靶标介导的衰变促进胃癌进展

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作者:Zhengyi Zhang, Jingnan Pi, Dongling Zou, Xiaoshuang Wang, Jiayue Xu, Shan Yu, Ting Zhang, Feng Li, Xianxie Zhang, Hualu Zhao, Fang Wang, Dong Wang, Yanni Ma, Jia Yu

Abstract

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.

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