HDAC inhibitor misprocesses bantam oncomiRNA, but stimulates hid induced apoptotic pathway

• Published in: Scientific reports 2015-10, Vol.5 (1), p.14747-14747, Article 14747
• Main Authors: Bhadra, Utpal, Mondal, Tanmoy, Bag, Indira, Mukhopadhyay, Debasmita, Das, Paromita, Parida, Bibhuti B., Mainkar, Prathama S., Reddy, Chada Raji, Bhadra, Manika Pal
• Format: Article
• Language: English
• Subjects: 59; 631/67; 631/67/2195; 64; 64/24; 96; 96/31; 96/35; 96/98; Animals; Apoptosis; Apoptosis - drug effects; Cancer; Caspase; Caspase-3; Cell death; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Embryogenesis; Embryonic growth stage; Histone deacetylase; Histone Deacetylase Inhibitors - chemistry; Histone Deacetylase Inhibitors - pharmacology; Homeostasis; Humanities and Social Sciences; Humans; Immunodeficiency; Insects; MicroRNAs; MicroRNAs - genetics; miRNA; Mitochondria; multidisciplinary; Neuropeptides - genetics; Neuropeptides - metabolism; Proto-Oncogene Proteins - genetics; Science; Signal Transduction - drug effects; Tumor cell lines; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep14747

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.