Membrane‐anchored E‐cadherin/AGO2 complex promote non‐canonical miRNA biogenesis of miR‐451a

Abstract

Micro‐RNAs are small non‐coding RNAs which regulate target mRNAs expression. Canonical miRNA biogenesis requires two‐step processing conducted by Drosha/DGCR8 and Dicer/AGO2 complexes in the nucleus and cytoplasm, respectively. Aberrant miRNA biogenesis have been reported in malignant human cancers. E‐cadherin is a junctional protein which localizes on plasma membrane to maintain cell‐cell adhesion. Downregulation of E‐cadherin is widely observed in cancers and correlates with epithelial–mesenchymal transition (EMT), it maintains cell‐cell contact and epithelial‐like phenotype to suppress migratory and invasive abilities of cancer cells. Although abnormal regulation of miRNA biogenesis has been reported in cancer, the integrated spatial and temporal regulatory pathways remains unclear. Here, we study the physical interaction between E‐cadherin and AGO2, and the effects on miRNA biogenesis. We found that E‐cadherin enhance the accumulation of AGO2 protein on cell membrane. Membrane‐anchored E‐cadherin/AGO2 complex promotes AGO2‐mediated specific miRNA, miR‐451a, biogenesis in a Dicer‐independent manner. Furthermore, the induced miR‐451 targeted EPH receptor A6 (EphA6) 3′UTR and downregulated EphA6, a metastasis‐promoting gene family member in breast cancer. Our findings demonstrate the spatial and temporal regulation of an AGO2‐dependent miRNA biogenesis pathway modulated by E‐cadherin, which provides new insight into the reciprocal interaction between EMT and miRNA biogenesis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.