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Tumor suppressor p53 induces miR‐1915 processing to inhibit Bcl‐2 in the apoptotic response to DNA damage
Author(s) -
Nakazawa Kazuya,
Dashzeveg Nurmaa,
Yoshida Kiyotsugu
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12831
Subject(s) - dna damage , downregulation and upregulation , suppressor , apoptosis , cancer research , biology , microrna , programmed cell death , dna , microbiology and biotechnology , cancer , chemistry , gene , genetics
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 mi RNA . Taken together, the findings of the current study reveal a novel mechanism whereby p53 negatively modulates Bcl‐2 by controlling miR‐1915.