sue from mice and zebrafish to see what happened when KRAS was activated.
Every time, the team noted the same robust findings. When KRAS was activated, the microRNA cluster miR-143/145 was powerfully repressed, to a fraction of the levels in normal, non-cancerous cells. Restoring the expression of miR-143/145 back to the level of normal cells was sufficient to confer "a very striking change in behavior of those cells," Mendell says. When human pancreatic cancer cells with low microRNA levels were injected into mice, they formed tumors within 30 days. However, when the team restored the levels of microRNAs to the levels of normal cells and injected them into mice, tumors failed to form.
"Our findings showed that repression of the miR-143/145 microRNA cluster is a very important component of the tumor-promoting cellular program that is activated when KRAS is mutated in cancer cells," says Oliver Kent, a postdoctoral fellow in the Mendell laboratory and first author on the paper.
At some point in the process of a normal cell evolving into a tumor cell, it loses microRNAs. When the KRAS gene is mutated a common event in pancreatic cancer it somehow purges cells of miR-143/145, the cluster of microRNAs that normally put the brakes on tumorigenesis.
"It is likely that some microRNAs will have very broad antitumorigenic effects in many different types of cancers," says Mendell, whose lab is building animal models to investigate how different microRNAs participate in different tumor types. "In fact, there is already evidence that miR-143/145 can suppress other types of tumors such as colon and prostate cancer. On the other hand, the effects of some microRNAs will likely be very tumor-specific."
Merely 22 nucleotides in length, microRNAs are enigmatic bits of genetic material that, despite being pint-sized, apparently are mighty. This field of study is less than a decade old; scientists still don't have a good gras
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| Contact: Maryalice Yakutchik myakutc1@jhmi.edu 443-287-2251 Johns Hopkins Medical Institutions Source:Eurekalert |
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