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DRAIC is a 1.7 kb spliced long noncoding RNA down-regulated in
castration-resistant advanced prostate cancer. Decreased DRAIC
expression predicts poor patient outcome in prostate and seven other
cancers while increased DRAIC represses growth of xenografted tumors.
When investigating the mechanism of action of DRAIC, we noted that
cancers with decreased DRAIC expression showed increased NF-kB target
gene expression. DRAIC downregulation increases cell invasion and soft
agar colony formation, and this requires NF-kB activation. DRAIC
interacts with subunits of IkB kinase (IKK) complex to inhibit their
interaction with each other, inhibit the phosphorylation of IkBα and
the activation of NF-kB. All these actions of DRAIC map to the same
fragment containing bases 701-905. Thus, DRAIC lncRNA inhibits prostate
cancer progression through suppression of NF-kB activation by
interfering with IKK activity |