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

Zhang Z1,2,3, Pi J1,2,3, Zou D4, Wang X1,2,3, Xu J1,2,3,5, Yu S1,2,3, Zhang T6, Li F7, Zhang X1,2,3, Zhao H1,2,3, Wang F1,2,3, Wang D8, Ma Y9,10,11, Yu J12,13,14
Nat Commun. 2019 Sep 27;10(1):4397
PMID: 31562301
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.