lung cancer tumors in mice
A small RNA molecule, known as let-7 microRNA (miRNA), substantially reduced cancer growth in multiple mouse models of lung
cancer, according to work by researchers at Yale and Asuragen Inc., published
in the journal Cell Cycle. — By Janet Rettig Emanuel
T H I S
Cancer afflicts 1.5 million people a year in the United States alone, and lung
cancer is the most common and deadly form of cancer worldwide. This study indicates
a direct role for a miRNA in cancer progression and introduces a new paradigm
of using miRNAs as effective therapeutic agents to treat human cancer.
“We believe this is the first report of a miRNA being used to a beneficial
effect on any cancer, let alone lung cancers, the deadliest of all cancers worldwide,” says
senior author Frank Slack, associate professor of molecular, cellular and developmental
biology at Yale.
Slack’s research group initially discovered the let-7 miRNA in C. elegans,
a tiny worm used as a model system for studying how organisms develop, grow
and age. They went on to show that in humans, let-7 negatively regulates a
well-known determinant of human lung cancers, the RAS oncogene.
In collaboration with scientists at Asuragen, the Slack lab has studied the
tumor suppressor activity of this small RNA. Their work revealed that let-7
is commonly present at substantially reduced levels in lung tumors — and
that reduced levels of let-7 likely contribute to the development of the tumors.
These discoveries focused public attention and research efforts to understand
the potential use of naturally occurring microRNAs like let-7 to combat cancer.
This new work demonstrates that let-7 inhibits the growth of lung cancer cells
in culture and in lung tumors in mice. They also showed that let-7 can be applied
as an intranasal drug to reduce tumor formation in a RAS mouse model lung cancer.
“We believe that our studies provide the first direct evidence in mammals
that let-7 functions as a tumor suppressor gene,” says Slack. “Because
multiple cell lines and mouse models of lung cancer were used, it appears that
therapeutic application of let-7 may provide benefits to a broad group of lung
cancer patients.”
Matt Winkler, chief executive officer of Asuragen, notes: “This has been
a very productive industry-academic collaboration between Yale and Asuragen
scientists. This work provides further evidence of the importance of miRNAs
in the development of cancer and provides additional support for miRNA replacement
therapy as an important component of effective cancer treatment regimens of
the future.”
Other authors on the paper were Aurora Esquela-Kerscher, Phong Trang and Joanne
Weidhaas at Yale; Jason Wiggins, Lubna Patrawala, David Brown and Andreas Bader
at Asuragen Inc.; and Angie Cheng and Lance Ford at Ambion Inc. The work was
funded by a grant from the State of Connecticut Department of Public Health
and fellowships from the National Institutes of Health.
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RNA molecule found to suppress lung cancer tumors in miceENDOWED PROFESSORSHIPS
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