OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer.
MicroRNAs (miRNA) 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 that 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. Cancer Res; 76(13); 3666-70. ©2016 AACR.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut.
Alexander A
AA
Svoronos
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut. fslack@bidmc.harvard.edu donald.engelman@yale.edu.
Donald M
DM
Engelman
Institute for RNA Medicine, Departments of Pathology and Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts. fslack@bidmc.harvard.edu donald.engelman@yale.edu.
Frank J
FJ
Slack
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D009857:Oncogenes / Q000235:genetics*
D035683:MicroRNAs