Dataset Information

MiR-15 and miR-16 induce apoptosis by targeting BCL2.

ABSTRACT: Chronic lymphocytic leukemia (CLL) is the most common human leukemia and is characterized by predominantly nondividing malignant B cells overexpressing the antiapoptotic B cell lymphoma 2 (Bcl2) protein. miR-15a and miR-16-1 are deleted or down-regulated in the majority of CLLs. Here, we demonstrate that miR-15a and miR-16-1 expression is inversely correlated to Bcl2 expression in CLL and that both microRNAs negatively regulate Bcl2 at a posttranscriptional level. BCL2 repression by these microRNAs induces apoptopsis in a leukemic cell line model. Therefore, miR-15 and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors.

SUBMITTER: Cimmino A

PROVIDER: S-EPMC1236577 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-15 and miR-16 induce apoptosis by targeting BCL2.

Cimmino Amelia A Calin George Adrian GA Fabbri Muller M Iorio Marilena V MV Ferracin Manuela M Shimizu Masayoshi M Wojcik Sylwia E SE Aqeilan Rami I RI Zupo Simona S Dono Mariella M Rassenti Laura L Alder Hansjuerg H Volinia Stefano S Liu Chang-Gong CG Kipps Thomas J TJ Negrini Massimo M Croce Carlo M CM

Proceedings of the National Academy of Sciences of the United States of America 20050915 39

Chronic lymphocytic leukemia (CLL) is the most common human leukemia and is characterized by predominantly nondividing malignant B cells overexpressing the antiapoptotic B cell lymphoma 2 (Bcl2) protein. miR-15a and miR-16-1 are deleted or down-regulated in the majority of CLLs. Here, we demonstrate that miR-15a and miR-16-1 expression is inversely correlated to Bcl2 expression in CLL and that both microRNAs negatively regulate Bcl2 at a posttranscriptional level. BCL2 repression by these microR ...[more]

PMID: 16166262

Similar Datasets

Project description:BackgroundMicroRNAs (miRNAs) function as endogenous regulators of biological behaviors of human cancers. Several natural non-coding RNAs are reported to inhibit miRNAs by base-pairing interactions. These phenomena raise questions about the ability of artificial device to regulate miRNAs. The purpose of this study is to create synthetic devices that target a single miRNA or a miRNA cluster and to ascertain their therapeutic effects on the phenotypes of bladder cancer cells.Methodology/principal findingsTandem bulged miRNA binding sites were inserted into the 3' untranslated region (UTR) of the SV-40 promoter-driven Renilla luciferase gene to construct two "miRNA-mowers" for suppression of miR-183-96-182 cluster or miR-210. A third device with tandem repeat sequences not complementary to any known miRNA was generated as an untargeted-control. In functional analyses, bladder cancer T24 and UM-UC-3 cells were transfected with each of the three devices, followed by assays for detection of their impacts. Luciferase assays indicated that the activities of the luciferase reporters in the miRNA-mowers were decreased to 30-50% of the untargeted-control. Using Real-Time qPCR, the expression levels of the target miRNAs were shown to be reduced 2-3-fold by the corresponding miRNA-mower. Cell growth, apoptosis, and migration were tested by MTT assay, flow cytometry assay, and in vitro scratch assay, respectively. Cell growth inhibition, increased apoptosis, and decreased motility were observed in miRNA-mowers-transfected bladder cancer cells.Conclusions/significanceNot only a single target miRNA but also the whole members of a target miRNA cluster can be blocked using this modular design strategy. Anti-cancer effects are induced by the synthetic miRNA-mowers in the bladder cancer cell lines. miR-183/96/182 cluster and miR-210 are shown to play oncogenic roles in bladder cancer. A potentially useful synthetic biology platform for miRNA loss-of-function study and cancer treatment has been established in this work.

Dataset Information

MiR-15 and miR-16 induce apoptosis by targeting BCL2.

Publications

miR-15 and miR-16 induce apoptosis by targeting BCL2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets