Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster.

Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibit miR-2, miR-13 and miR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species (ROS) level to trigger apoptotic cell death.

Expression and functional perspectives of miR-184 in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors, with its 5-year survival rate lower than 5%. MicroRNAs (miR) have been known as important regulators for the tumorigenesis, progression, invasion and metastasis of various cancers. MiR-184 was found to be abnormally expressed in various cancers including glioma and oral carcinoma. The expression and functional role of miR-184 in PDAC, however, remains unclear. PDAC cell line PANC-1 was transfected with miR-184 inhibitor. Real-time PCR was used to detect the expression of miR-184 in untreated PANC-1, miR-184 inhibitor transfected PANC-1 and controlled normal pancreatic ductal epithelial cell line HPDE6c7. MTT assay was used to detect the effect of miR-184 on the proliferation of PANC-1 cells, while invasion assay and Western blotting were employed to describe the effect on cell invasion ability and expression of caspase-3, respectively. In PANC-1 cells, miR-184 was abundantly expressed. The transfection of inhibitor effectively suppressed the expression of miR-184, and further inhibited both cell proliferation and invasion abilities, in addition to the up-regulation of pro-apoptotic protein caspase 3 expression. The up-regulation of miR-184 in PDAC may facilitate the proliferation and invasion ability, and inhibit apoptosis of tumor cells, thus potentiating the occurrence and development of PDAC. MiR-184, therefore, is a potential molecular target for therapy.