Synthetic regulation apoptosis. This pathway relies on the formation of a complex
termed the apoptosome, which is composed of procaspase-9, apoptotic protease
activating factor 1 (Apaf-1), and cytochrome c. A series of Bcl-2 family members
including Bax, Bak, Bcl-2, Bcl-xL, Mcl-1, Bid, and Bim control the release of
cytochrome c by regulating mitochondrial membrane permeabilization. MiR-365
directly targets the adaptor protein Src homology 2 domain-containing 1 (SHC1)
and the pro-apoptotic protein Bax. MiR-125b suppresses the pro-apoptotic Bak
expression. MiR-491 directly targets Bcl-xL and significantly decreases the
viability of cancer cells by inducing apoptosis. MiR-133a with its tumor-
suppressive activity is down-regulated in some cancer cells likely due to the
targeted suppression of Bcl-xL and Mcl-1 expression, and this down-regulation
strongly correlated with tumor progression and prognosis. MiR-608 targets Bcl-x
and is down-regulated in cancer cells. MiR-15a and miR-16–1 are downregulated
in cancer cells, and their expression inversely correlated with Bcl-2 expression.
MiR-204 is another suppressor of Bcl-2 expression and is down-regulated in
cancer cells. MiR-148a and miR-24–2c also directly suppress Bcl-2 expression.
MiR-23a/b and miR-27a/b act as endogenous inhibitors of Apaf-1 expression and
control the sensitivity of neurons to apoptosis. MiR-133 and miR-24a
observed to directly repress caspase-9 to regulate cell fate.