repaired or ending it all if repair isn’t
possible (SN: 12/6/08, p. 22). Last year
researchers reported in Nature that p53
helps slice microRNAs into their mature
form. Too much miR- 21 can strip cells of
their p53 defenses, leading to cancer.
4
3
Though miR- 21 has stood out among
the troublemakers, Croce’s team has
shown that this microRNA and others
don’t work alone. The molecular managers are master networkers. In 50 different normal human tissues, microRNAs
collaborate to direct cellular activities,
Croce and colleagues reported online
May 3 in Genome Research. The networks consist of microRNAs that help
direct production of proteins, some of
which, in turn, control production of
other microRNAs, and so on.
Relative level
2
1
But time and again, in 51 different
types of cancer, Croce’s team found that
the microRNAs’ teamwork had broken
down. The cohesive networks disintegrated into rogue hubs of activity. These
anarchist factions throw a wrench into
the well-oiled machinery that usually
keeps a cell healthy.
It’s a rather small wrench, though.
MicroRNAs wield their power subtly,
tweaking and massaging protein levels up
or down a wee bit here and there instead
of stopping production altogether.
“A microRNA doesn’t function like an
‘off’ switch,” says cancer biologist Dihua
Yu of the University of Texas MD Anderson Cancer Center in Houston.
Even a little bump or dip in protein
5
MicroRNA levels and cancer aggressiveness
0
source: G. mArtello et al/cell 2010
More aggressive cancers Nonspreading
cancer
Getting a move on imbalances in
micrornA levels can spur cancer cells to
spread. too much mir-103 or mir-107 has been
linked to increased mobility among cancer cells.
miR-103
miR-107
microRNAs, allowing more of the protein to be made. If the twin is missing,
the weight of micro RNAs on messenger
RNA’s back can crush protein production.
New research from Yu’s lab also suggests that reducing the amount of P TEN
protein in a tumor cell even slightly is
not a good idea. Higher levels of miR- 21
slow down PTEN production and make
breast cancer cells resistant to an anti-cancer agent called Herceptin, Yu and
colleague Sumaiyah Rehman reported
in April in Washington, D.C., at the
annual meeting of the American Association for Cancer Research.
levels, maybe by just 5 to 10 percent, is
enough to send a cell careening down the
path to cancer, Croce says.
One of the most delicately balanced
cancer-associated proteins is PTEN.
It reins in cell growth to prevent wild
replication, as seen in cancer. In the
parlance of cancer research, PTEN is
known as a tumor suppressor, and it
works best when there is just the right
amount of it.
Losing one copy of the gene for
PTEN — essentially cutting protein levels
in half — is enough to turn a cell cancerous, previous studies have shown. Other
research has demonstrated that microRNAs, including miR- 21, help govern production of PTEN. And a study reported
June 24 in Nature found that a messenger RNA doppelgänger of PTEN found
in healthy cells distracts PTEN-stifling
Gene for: miR-146a miR-196a miR-423 miR-27a miR-492 miR-499
Lung cancer X
Esophageal
cancer X X
Breast cancer X X X X
Stomach cancer X
Liver cancer XX
Bladder cancer X X
Papillary thyroid X
Brain cancer X
Little differences some studies have linked single letter changes in the genes encoding
micrornAs to various types of cancer. Genetic variations in the genes may interfere with the
production or function of the molecules.
source: B.m. ryAn et al/nature reviews cancer 2010
Variations in microRNA genes linked to cancers
Dicer danger
