| microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression posttranscriptionally by interfering with the translation of one or more target mRNAs. The
unique miRNA sequences are involved in many physiological and pathological
processes. Dysregulation of miRNAs contributes to the pathogenesis of all types of
cancer. Notably, the diminished expression of tumor suppressor miRNAs, such as
members of the Let-7 and miR-34 family, promotes tumor progression, invasion and
metastasis. The past lustrum in particular, has witnessed substantial improvement of
miRNA replacement therapy. This approach aims to restore tumor suppressor miRNA
function in tumor cells using synthetic miRNA mimics or miRNA expression plasmids.
Here, we provide a comprehensive review of recent advances in miRNA replacement
therapy for treatment of cancer and its advantages over conventional gene therapy. We
discuss a wide variety of delivery methods and vectors, as well as obstacles that remain
to be overcome. Lastly, we review efforts to reverse epigenetic alterations, which affect
miRNA expression in cancer cells, and the promising observation that restoring miRNA
function re-sensitizes resistant tumor cells to chemotherapeutic drugs. The fact that
various miRNA replacement therapies are currently in clinical trial demonstrates the
great potential of this approach to treat cancer. |