Downregulation of miR-21 as a promising strategy to overcome drug resistance in cancer.

Despite tremendous achievements in the field of targeted cancer therapy, chemotherapy is still the main treatment option, which is challenged by acquired drug resistance. Various microRNAs are involved in developing drug-resistant cells. miR-21 is one of the first identified miRNAs involved in this process. Here, we conducted a literature review to categorize different mechanisms employed by miR-21 to drive drug resistance. miR-21 targets various genes involved in many pathways that can justify chemoresistance. It alters cancer cell metabolism and facilitates adaptation to the new environment. It also enhances drug detoxification in cancerous cells and increases genomic instability. We also summarized various strategies applied for the inhibition of miR-21 in order to reverse cancer drug resistance. These strategies include the delivery of antagomiRs, miRZip knockdown vectors, inhibitory small molecules, CRISPR-Cas9 technology, catalytic nucleic acids, artificial DNA and RNA sponges, and nanostructures like mesoporous silica nanoparticles, dendrimers, and exosomes. Furthermore, current challenges and limitations in targeting miR-21 are discussed in this article. Although huge progress has been made in the downregulation of miR-21 in drug-resistant cancer cells, there are still many challenges to be resolved. More research is still required to find the best strategy and timeline for the downregulation of miR-21 and also the most feasible approach for the delivery of this system into the tumor cells. In conclusion, downregulation of miR-21 would be a promising strategy to reverse chemoresistance, but still, more studies are required to clarify the aforementioned issues.