Artificial miRNAs derived from miR‐181 family members have potential in cancer therapy due to an altered spectrum of target mRNAs

miRNAs are a class of noncoding RNAs with gene regulation properties, and they function as key factors in cell homeostasis. The interaction of miRNAs with their target mRNAs is largely considered to rely on sequence complementarity; however, some evidence indicates that mature miRNAs can adopt diverse conformations with implications for their function. Using the oncogenic miR‐181 family as a study model, we suggest that a potential relationship between the primary sequence and secondary structure of miRNAs may have an impact on the number and spectrum of targeted cellular transcripts. We further emphasize that specific alterations in miR‐181 primary sequences might impose certain constraints on target gene selection compared with the wild‐type sequences, leading to the targeting of new transcripts with upregulated function in cancer. Native miRNAs regulate diverse cellular processes by targeting a broad spectrum of genes. Specific alterations in the primary sequence of native miRNA sequences might result in conformational changes which are associated with a reduced number of target genes, that might include tumor promoting genes. These artificial miRNAs might represent novel RNA‐based therapies for cancer treatment.