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

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.

Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival

“…A limited number of studies have investigated the functions of both miRNA strands of specific miRNA in specific cancers [10][11][12][13][14][15][16][17][18][19][20] . For example, miR-31-5p and miR-31-3p are both upregulated in oral squamous cell carcinoma, but one counteracts the oncogenic function of the other 17 .…”

The potential role of miR-21-3p in coronavirus-host interplay

“…A similar concept was named as target RNA directed miRNA degradation (TDMD) which consists of the fact that highly complementary target RNA can trigger miRNA degradation by a mechanism involving nucleotide addition and exonucleolytic degradation (la Mata et al, 2015). This concept was experimentally validated as an example of miR-574-5p and miR-574-3p study in gastric cancer (Zhang et al, 2019). Thus, non-proportional up-regulation of miR-21 arms can be indirect evidence that miR-21-3p directly targets the viral RNA or that the miR-21-5p is being actively degraded during target mRNA binding.…”

Terminal Modification, Sequence, and Length Determine Small RNA Stability in Animals

“…miRNAs with extensively complementary targets are unstable-a phenomenon termed Target RNA-Directed miRNA Degradation (TDMD; Cazalla et al, 2010;Ameres et al, 2010;Baccarini et al, 2011;Libri et al, 2012;Marcinowski et al, 2012;Rüegger and Großhans, 2012;Lee et al, 2013;de la Mata et al, 2015;Bitetti et al, 2018;Kleaveland et al, 2018;Ghini et al, 2018;Sheu-Gruttadauria et al, 2019a;Zhang et al, 2019). In most animals, miRNAs bear a 2′-hydroxyl at their 3′ terminus.…”