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.

ZnO Nanopillar Coated Surfaces with Substrate‐Dependent Superbactericidal Property

“…The average height of the nanopillar is about 1 µm (aspect ratio > 10) and the average interval is about 120 nm. This structural topology is consistent with those highly efficient bactericidal nanopatterned surfaces . Figure a–d shows the scanning electron microscope (SEM) images of ZnO nanopillars on glass, titanium and zinc foil (see supporting information for the images of ZnO nanopillar on other substrates, Figure S1 in the Supporting Information).…”

“…Recently, it was reported that cicada and dragonfly wing surfaces are covered with dense patterns of nanoscale pillar arrays that prevent bacterial growth by rupturing adhered microbial cells . It was also proved that a purely physical interaction between the cells and synthetic nanopatterns such as black silicon surfaces also results in cell deformation and massive lysis without the need for additional external chemicals or mechanical intervention . This new discovery opens up a great opportunity for the development of innovative microbicide surface technologies which are clean and safe, require no external chemicals and have no resistance issue.…”

“…The microbicide properties of the nanostructures on the surfaces of black silicon, TiO 2 , polymer, and gold have been demonstrated . These surfaces with nanopatterns were generally prepared by a top‐down approach on specific materials.…”

Pygmy MicroRNA: Surveillance Cops in Therapy Kingdom

“…Experimental evidence has shown that several cell cycle genes along with checkpoint kinase1-targeted cardiomyocyte proliferation can occur by regulation of miR-195 (107). Interestingly, miR-195 inhibition by LNA-modified anti-miRs in pigs and mice showed steady effects on heart regeneration, whereas treated animals were devoid of myocardial infarction (108 (86,87). Experimental data support that the mitochondrial regulatory pathway in human cancer cell lines can be affected by HDAC inhibitor, which suggests a conservative feature of apoptosis between Drosophila and humans.…”

Selective HDAC inhibitors with potent oral activity against leukemia and colorectal cancer: Design, structure-activity relationship and anti-tumor activity study

“…The class III HDACs (comprising SIRT 1-7) are related to the yeast protein Sir2 and their activities are depended on NAD + concentration [4,5]. The exact physiological role of these HDAC subtypes in cells is far from being completely elucidated, however, the division of labor among them has been studied using knockout and transgenic mice and RNAi techniques, in which, class I and class II are the most well studied [6,7]. The knockout of HDAC1 in mice caused cell proliferation defects and developmental retardation, and this unique function cannot be compensated by HDAC2 and HDAC3 [8,9].…”