title: HDAC inhibitor misprocesses bantam oncomiRNA, but stimulates hid induced apoptotic pathway.
abstract: Apoptosis or programmed cell death is critical for embryogenesis and tissue homeostasis. Uncontrolled apoptosis leads to different human disorders including immunodeficiency, autoimmune disorder and cancer. Several small molecules that control apoptosis have been identified. Here, we have shown the functional role of triazole derivative (DCPTN-PT) that acts as a potent HDAC inhibitor and mis-express proto onco microRNA (miRNA) bantam. To further understanding the mechanism of action of the molecule in apoptotic pathway, a series of experiments were also performed in Drosophila, a well known model organism in which the nature of human apoptosis is very analogous. DCPTN-PT mis processes bantam microRNA and alters its down regulatory target hid function and cleavage of Caspase-3 which in turn influence components of the mitochondrial apoptotic pathway in Drosophila. However regulatory microRNAs in other pro-apoptotic genes are not altered. Simultaneously, treatment of same molecule also affects the mitochondrial regulatory pathway in human tumour cell lines suggesting its conservative nature between fly and human. It is reasonable to propose that triazole derivative (DCPTN-PT) controls bantam oncomiRNA and increases hid induced apoptosis and is also able to influence mitochondrial apoptotic pathway.
authors.affiliation: Functional Genomics and Gene silencing group, CSIR-Centre for Cellular &Molecular Biology, Uppal Road, Hyderabad 500007, INDIA.
authors.forename: Utpal
authors.initials: U
authors.lastname: Bhadra
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, INDIA.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Mondal
authors.affiliation: Functional Genomics and Gene silencing group, CSIR-Centre for Cellular &Molecular Biology, Uppal Road, Hyderabad 500007, INDIA.
authors.forename: Indira
authors.initials: I
authors.lastname: Bag
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, INDIA.
authors.forename: Debasmita
authors.initials: D
authors.lastname: Mukhopadhyay
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, INDIA.
authors.forename: Paromita
authors.initials: P
authors.lastname: Das
authors.affiliation: Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, INDIA.
authors.forename: Bibhuti B
authors.initials: BB
authors.lastname: Parida
authors.affiliation: Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, INDIA.
authors.forename: Prathama S
authors.initials: PS
authors.lastname: Mainkar
authors.affiliation: Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, INDIA.
authors.forename: Chada Raji
authors.initials: CR
authors.lastname: Reddy
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, INDIA.
authors.forename: Manika Pal
authors.initials: MP
authors.lastname: Bhadra
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D056572:Histone Deacetylase Inhibitors; D035683:MicroRNAs; D009479:Neuropeptides; D011518:Proto-Oncogene Proteins; C471146:bantam microRNA, Drosophila