cancer index. mice injected with breast cancer cells make a lot of a long strand of RNA called Hotair developed 10 times more lung tumors as controls ( left ) did.
Adapted from Gupta et al., Nature, 464 (15 April 2010)
Researchers say they have discovered a new molecular player to determine whether cells breast cancer spreads through the body: long strands of RNA called lincRNAs who suppress tumor suppressor genes. The finding may lead to a test to predict metastasis and medication to prevent.
Several factors determine whether the cells will become cancerous and later go mobile. Mutations in tumor suppressor genes such as p53 and BRCA1 play a role, as "microRNA" genes that critics of silence.
Problems with lincRNAs appear to be another mechanism. The researchers first identified lincRNAs-short for intervening noncoding RNAs are big-9 years. Often, hundreds or thousands of times longer than the microRNA, which run approximately 22 nucleotides, some lincRNAs seem to influence the expression of genes by binding to enzymes that modify chromatin, the DNA-protein packet that makes up chromosomes . The lincRNAs run these enzymes chromatin formatting to specific sites along the chromosomes, where they Tack chemical groups on genes, blocking them from being expressed. A lincRNA known Hotair, for example, helps tell embryonic skin cells that express genes based on their location in the body.
Because some cancer genes arose in this working skin cells, cancer biologist Howard Chang of Stanford University began exploring whether Hotair and other lincRNAs could also play a role in the cancer. His group and colleagues eventually hosted in the Hotair in samples of human breast cancer. Hotair levels were hundreds of times higher than normal in samples of metastatic breast cancer, the researchers found, and they were sometimes unusually high in primary tumors. Looking at samples from 132 women with breast cancer followed for many years, the team also found that women with high levels Hotair in their primary tumor were three times more likely to develop metastatic cancer and die.
For more details, Chang's team used modified virus to ramp up Hotair expression in breast cancer cells. When inserted into the tail of mice, these cells caused high Hotair 10 times more metastatic tumors in the lungs than unmodified cancer cells. Hotair apparently promotes metastasis by closing the genes involved in the conservation of cells to move. With these extinct genes, primary tumor cells can more easily invade the cell matrix surrounding organs and form metastatic tumors, said Chang, whose team reports its findings in tomorrow's edition of Nature .
A test for Hotair levels could be used to predict which patients with breast cancer will develop metastases, the authors suggest. Hotair and blocking the enzyme, it interacts with could be a way to prevent metastasis.
The general message is that microRNAs are not the only type of non-coding RNAs that researchers should be careful when it comes to how the cancer spreads, says George Calin MD Anderson Cancer Center in Houston, Texas. "It opens a new research field."
molecular geneticist Maarten van Lohuizen of the Netherlands Cancer Institute in Amsterdam agreed that the study is "important and provocative." But he notes that it raises many questions. For example, he wonders why would Hotair of such profound effects when it is just one of many lincRNAS present at high levels in metastatic tumors.
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