The miRNA-9 Isoform Story in Cancer: An OncomiR or Tumor Suppressor?

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally. They function by binding to newly transcribed mRNAs of protein-coding genes, suppressing gene expression at the post-transcriptional level. Thus, miRNAs play a crucial role in controlling a plethora of cellular processes, making miRNAs a unique class of regulatory RNA with defined developmental roles. Thus, these small yet powerful miRNAs have garnered the attention of many researchers due to the known biological regulatory role during chronic disease onset, including cancer. Over the past decade, novel small RNA therapies have been developed and implemented successfully in the clinic to combat several chronic disorders. With respect to cancer, a number of miRNAs were demonstrated to be correlated with cancer progression and disease onset. These oncomiRs or tumor suppressors control well conserved protein signaling cascades that become dysregulated during the tumorigenic process. In particular miR-9 has garnered much attention over the past decade due to the abundance of this miRNA in certain tissues such as the brain and the epithelium. In this review, we discuss the importance of miRNAs in cancer, the biology of miR-9 in a variety of cancers, explain how the term ‘oncomiR’ or ‘tumor suppressor miR’ depends upon the cellular context of gene expression during oncogenesis, and how the abundance of certain miR-9 isoforms in the cell during the initiating tumorigenic event could influence the molecular heterogeneity of the tumor. Additionally, next-generation miRNA therapeutics offer promising strategies for cancer treatment by the precise targeting of disease-related pathways with minimal toxicity and off-target effects. These strategies can also serve as solutions in situations where chemo- and radio-resistance persists.