title: Tumor suppressor p53 induces miR-1915 processing to inhibit Bcl-2 in the apoptotic response to DNA damage.
abstract: The antiapoptotic protein Bcl-2 is overexpressed in human cancers, and confers resistance to antitumor agents in cancer cells. Bcl-2 is negatively regulated by the tumor suppressor p53 in response to DNA damage during apoptotic cell death. However, this molecular mechanism remains unclear. The available evidence indicates that miR-1915 represses Bcl-2 expression at the post-transcriptional level in human colorectal carcinoma cells, which is correlated with drug resistance. Here, we show that p53 controls miR-1915 expression in response to DNA damage. Induction of p53 affects the expression of precursor and mature, but not primary, miR-1915. Inhibition of miR-1915 abrogates downregulation of Bcl-2 expression following treatment with genotoxin. These findings demonstrate that p53 negatively regulates Bcl-2 expression by targeting miR-1915 processing from primary into precursor miRNA. Taken together, the findings of the current study reveal a novel mechanism whereby p53 negatively modulates Bcl-2 by controlling miR-1915.
authors.affiliation: Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan; Medical Research Institute, Tokyo Medical and Dental University, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Nurmaa
authors.initials: N
authors.lastname: Dashzeveg
authors.forename: Kiyotsugu
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D004249:DNA Damage; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: C578402:MIRN1915 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Bcl-2; DNA damage; apoptosis; miR-1915; p53