To summarize, we propose that plant RDR1 with nucleotidyltransferase activity is able to add mononucleotide tails to the 1-nt-shorter miRNA duplex isoforms, which is dissociated from AGO2 and accumulated in cancer cells and enhances the AGO2 loading efficiency to finally rescue the defective miRNA pathway in cancer cells (Figure 1). This evidence concerns the gene AGO2 and cancer.