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.

Automated summary

miRNAs are noncoding RNAs that regulate genes and play a key role in cell homeostasis. The interaction between miRNAs and their target mRNAs is believed to depend on sequence complementarity, but some evidence suggests that miRNAs can adopt different structures that affect their function. By studying the oncogenic miR-181 family, we propose that the primary sequence and secondary structure of miRNAs may impact the number and range of targeted cellular transcripts. We also highlight that specific changes in miR-181 primary sequences may limit target gene selection and lead to the targeting of new transcripts with enhanced cancer-related functions.