An oncogene is a gene that, when mutated, can cause cancer. The mutated gene creates a malfunctioning protein that encourages a cell to divide uncontrollably or enables it to sidestep the normal breakpoints that would halt cell division or launch a cellular suicide program to protect the organism.

The KRAS protein is a product of an oncogene. The protein sits on a cell’s outer membrane and functions as an on-off switch to control cell division. Normally, it helps cells respond appropriately to external signals calling for cell growth. When mutated, however, it encourages the cell to undergo repeated rounds of cell division. KRAS mutation is an essential step in the development of nearly all human cancers.

The RNAs studied by the researchers are small, noncoding RNAs known as snoRNAs. Unlike the more familiar messenger RNA molecules that carry protein-making instructions from the DNA in the nucleus to the outer cellular machinery called ribosomes, noncoding RNAs fulfill other necessary cellular functions. SnoRNAs are known to help assemble the ribosomes themselves.

They compared 5,473 tumor genomes with the genomes obtained from surrounding normal tissue in 21 different types of cancer. In many ways, cancer cells represent biology’s wild west. These cells divide rampantly in the absence of normal biological checkpoints, and, as a result, they mutate or even lose genes at much higher rate than normal. As errors accumulate in the genome, things go ever more haywire.

The researchers found that a pair of snoRNAs called SNORD50A/B had been deleted in 10 to 40 percent of tumors in 12 common human cancers, including skin, breast, ovarian, liver and lung. They also noted that breast cancer patients whose tumors had deleted SNORD50A/B, and skin cancer patients whose tumors made lower levels of the RNAs than normal tissue, were less likely than other similar patients to survive their disease. 
 
Researchers found that these RNAs associate with proteins in the RAS family, and specifically KRAS. When they deleted SNORD50A/B in human melanoma and lung cancer cells grown in the lab, the cells divided more quickly and displayed more cancerous traits than when SNORD50A/B was present.

Finally, they showed that when SNORD50A/B binds to KRAS, it inhibits the protein’s ability to associate with an activating molecule called farnesyltransferase. Farnesyltransferase modifies the KRAS protein in such a way to allow it to travel to the cell’s membrane to await external signals for growth and division.  

When the genes for SNORD50A/B are lost from the genome, KRAS is free to goad the tumor cells to undergo repeated rounds of cell division. The research is published in the journal Nature Genetics.

http://med.stanford.edu/news/all-news/2015/11/new-class-of-rna-tumor-suppressors-identified-by-researchers.html