Protective Role Of MicroRNA

Snippets of genetic material that have been associated with cancer also play a critical role in normal embryonic development in mice, as per a new paper from MIT cancer biologists.

The work, published in the March 7 issue of Cell, shows that a family of microRNAs--short strands of genetic material--protect mouse cells during development and allow them to grow normally. But that protective role could backfire: The scientists theorize that when these microRNAs become overactive, they can help keep alive cancer cells that should otherwise die--providing another reason to target microRNAs as a therapy for cancer.

Discovered only a decade ago, microRNAs bind to messenger RNAs (mRNAs), preventing them from delivering protein assembly instructions, thereby inhibiting gene expression. The details of how microRNAs act are still not fully understood.

"The scientific community is busy trying to understand what specific biological functions these microRNAs affect," said Andrea Ventura, lead author of the paper and postdoctoral associate in the Koch Institute for Integrative Cancer Research at MIT (formerly known as the Center for Cancer Research).

Ventura--who works in the laboratory of Tyler Jacks, director of the Koch Institute--and her colleagues studied the function of a family of microRNAs known as the miR-17~92 cluster.

Prior research has shown that the miR-17~92 cluster is overactive in some cancers, particularly those of the lungs and B cells.

To better understand these microRNAs' role in cancer, the scientists decided to study their normal function. Knocking out microRNA genes and observing the effects can offer clues into how microRNA helps promote cancer when overexpressed.

They observed that when miR-17~92 was knocked out in mice, the animals died soon after birth, apparently because their lungs were too small. Also, their B cells, a type of immune cell, died in an early stage of cell development.

This suggests that miR-17~92 is critical to the normal development of lung cells and B cells. In B cells, these microRNAs are likely acting to promote cell survival by suppressing a gene that induces cell death, said Ventura.

"Understanding why these things are happening provides important insight into how microRNAs affect tumorigenesis," he said.

The scientists theorize that when miR-17~92 becomes overactive in cancer cells, it allows cells that should undergo programmed cell death to survive.

Blocking microRNAs that have become overactive holds promise as a potential cancer therapy. Research is now being done on molecules that prevent microRNAs from binding to their target mRNA.

More work needs to be done to make these inhibitors into stable and deliverable drugs, but Ventura said it's possible it could be done in the near future.

The exact genes targeted by miR-17~92 are not known, but one strong suspect is a gene called Bim, which promotes cell death. However, a single microRNA can have a number of targets, so it's likely there are other genes involved.

The scientists also studied the effects of knocking out two other microRNA clusters that are closely correlation to miR-17~92 but located elsewhere in the genome.

They observed that if the other two microRNA clusters are knocked out but miR-17~92 remains intact, the mice develop normally. However, if miR-17~92 and one of these similar clusters are removed, the mice die before birth, suggesting there is some kind of synergistic effect between these microRNA families.


Posted by: Janet    Source