instructions from DNA to the ribosomes, where
proteins are built. The microRNAs pair up with
their larger messenger RNA mates and slate the
bigger molecules for destruction, or at least prevent their instructions from being translated into
proteins. One microRNA might have hundreds of
mates, or targets, through which it influences many
different body functions.
Lewis studies one gang of six microRNAs,
known as the miR- 17~92 cluster, the first group
of microRNAs found to play a role in cancer. The
six normally help strike a balance between cell
growth and death, but an imbalance of these little
molecules can push cells toward cancer.
Tumors in pancreatic cancer patients tend to
have elevated levels of the cluster. To learn what
the microRNAs were doing to goad cancer into
taking hold, Lewis and colleagues used a genetic
trick to remove the microRNAs from the pancreas in mice that were genetically engineered to
develop pancreatic tumors. Early in their lives,
mice with and without the microRNA cluster had
about the same number of precancerous cells.
But by the time the animals were 9 months
old, a clear difference emerged. In mice with the
miR- 17~92 microRNAs, nearly 60 percent of the
pancreas was tending toward cancer, compared
with less than 20 percent in mice lacking the cluster.
The finding, reported in 2017 in Oncotarget, suggests that the microRNAs aid the cancer’s start.
The researchers developed bits of RNA that
block some of the cluster members from spurring
on the tumor. Using human pancreatic cancer cells
grown in lab dishes, Lewis and colleagues found
that taking out two of the six cluster members,
miR-19a and miR-19b, stopped cancer cells from
forming structures called invadopodia. As their
name suggests, invadopodia allow tumors to break
through blood vessel walls and other barriers to
spread through the body.
Transfer RNA fragments
THE VIRUS HELPERS
For some young children and older adults, an
infection with respiratory syncytial virus, or RSV,
feels like a simple cold. But each year in the United
States, more than 57,000 children younger than
age 5 and about 177,000 people older than 65 are
hospitalized because of the virus, the U. S. Centers
for Disease Control and Prevention estimates.
The infection kills hundreds of babies and about
14,000 adults over 65 annually.
Slightly higher than normal levels of some
microRNAs had been linked to severe RSV infections. But molecular virologist Xiaoyong Bao
of the University of Texas Medical Branch in
Galveston wasn’t convinced that modestly
increasing amounts of a few microRNAs could
really mean the difference between a child getting
a slight cold and dying from the respiratory virus.
She consulted her Texas Medical Branch colleague, cancer researcher Yong Sun Lee, for advice
on studying microRNAs. Lee said Bao would need
to deeply examine, or sequence, RNA in cells
infected with the virus. That was an expensive
proposition in 2012 when Bao started the project.
“But I squeezed from my [lab’s] dry bank account,”
she says, to pay for the experiment. The investment paid off.
Cells infected with RSV had more of one
of transfer RNAs can
spur growth of respiratory syncytial virus, an
infection that’s most
dangerous in the elderly
and young children.