Is miR-34a a Well-equipped Swordsman to Conquer Temple of Molecular Oncology?

Abstract

Overwhelmingly increasing advancements in miRNA biology have opened new avenues for pharmaceutical companies to initiate studies on designing effective, safe, and therapeutically active candidates using miRNA mimetics and miRNA inhibitors. In accordance with this approach, development of miravirsen and SPC3649, an LNA-based (locked nucleic acid) antisense molecule against miR-122, to treat hepatitis C has sparked interest in identifying most efficient microRNAs for journey from bench-top toward pharmaceutical industry and breakthroughs in delivery technology will pave the way to final frontier'. MRX34, a liposome-formulated mimic of miR-34 for treatment of metastatic cancer with liver involvement and unresectable primary liver cancer, has also entered in clinical trial. There is a successive increase in the research work related to miR-34 biology and miRNA regulation of modulators of intracellular signaling cascades. We partition this review into how miR-34a is regulated by different proteins and how Wnt- and TGF-induced intracellular signaling cascades are modulated by miR-34a. In this review, we bring to limelight how miR-34a regulates its target genes to induce apoptosis and inhibit cell proliferation as evidenced by in vitro and in vivo analysis. We also discuss miR-34 regulation of PDGFR and c-MET and recent advancements in nanotechnologically delivered miR-34a. Spotlight is also set on modulation of chemotherapeutic sensitivity by miR-34a in cancer cells using reconstruction studies. Clinical trial of miR-34 is indicative of its tremendous potential, and continuous cutting research will prove to be effective in efficiently translating laboratory findings into clinically effective therapeutics.