OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer

Abstract

MicroRNAs are short, noncoding RNAs whose dysregulation has been implicated in most, if not all, cancers. They regulate gene expression by suppressing mRNA translation and reducing mRNA stability. To this end, there is a great deal of interest in modifying miRNA expression levels for the treatment of cancer. However, the literature is fraught with inconsistent accounts as to whether various miRNAs are oncogenic or tumor suppressive. In this review, we directly examine these inconsistencies and propose several mechanisms to explain them. These mechanisms include the possibility that specific miRNAs can simultaneously produce competing oncogenic and tumor suppressive effects by suppressing both tumor suppressive mRNAs and oncogenic mRNAs, respectively. In addition, miRNAs can modulate tumor-modifying extrinsic factors, such as cancer-immune system interactions, stromal cell interactions, oncoviruses, and sensitivity to therapy. Ultimately, it is the balance between these processes which determines whether a specific miRNA produces a net oncogenic or net tumor suppressive effect. A solid understanding of this phenomenon will likely prove valuable in evaluating miRNA targets for cancer therapy.

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

“…We also performed sequencing for secondary mutations in the ALK gene to interpret of our findings in the context of previously identified mechanisms of resistance ( Table 1). Among the eight samples available for ALK sequencing, 2 samples (25%) revealed the L1196M mutation, which is the (31)(32)(33)(34)). In the model described here, ceritinib-resistant cells exhibited an EMT phenotype with AXL activation.…”

Epigenetic regulation by DNA methylation and miRNA molecules in cancer

“…These opposite roles could be explained by the fact that miR-125b targets multiple mRNAs, it suppresses the hematopoietic differentiation factors in hematological malignancies that have a weak importance in a majority of solid tumors. MiRNA molecules are also involved in the interactions with cancer-immune system and other tumor-modifying extrinsic factors on which their expression in oncogenic or tumor-suppressive pathways depends [15].…”

Epigenetic Control of the Tumor Microenvironment

“…A large number of miRNAs have been identified in the human genome and each species of miRNA may have multiple mRNA targets [75]. Many individual miRNA species have been shown to play roles in the regulation of stromal cells of the tumor microenvironment and this subject has recently been reviewed [76][77][78][79].…”