title: 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.
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan.
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan.
authors.forename: Sundas
authors.initials: S
authors.lastname: Fayyaz
authors.affiliation: Diagnostic Imaging and Radiation Therapy Department, Lviv National Medical University, Lviv, Ukraine.
authors.forename: Iryna
authors.initials: I
authors.lastname: Shatynska-Mytsyk
authors.affiliation: Chughtai Lahore Lab (CLL), Lahore, Pakistan.
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Javed
authors.affiliation: Department of Zoology, PMAS-Arid Agriculture University, Rawalpindi, Pakistan.
authors.forename: Saima
authors.initials: S
authors.lastname: Jabeen
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
authors.affiliation: Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gasparri
authors.affiliation: Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Pierluigi Benedetti
authors.initials: PB
authors.lastname: Panici
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D015291:Transforming Growth Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D051153:Wnt Proteins; D015291:Transforming Growth Factors; D017479:Receptors, Platelet-Derived Growth Factor; D006655:Histone Deacetylases
keywords: Apoptosis; cancer; miR-34a