Researchers found that a losing a section of messenger RNA that was previously thought to transform normal cells into cancerous ones actually acts by blocking a body's ability suppress the formation of tumors. The finding could completely alter the way that medical science approaches the formation of tumors.
In molecules throughout the body, the three-prime untranslated region, or 3'UTR, is a section of messenger RNA that can alter gene expression. It's known that shortening this RNA section promotes cancerous tumor growth.
"Researchers have historically thought that this was because 3'UTR shortening induces the expression of proto-oncogenes, normal genes that when altered by mutation or expressed too high, become oncogenes that can transform a normal cell into a cancer cell," said the senior author. "However, using a combination of computational approaches and cancer cell models, we found that 3'UTR shortening in tumors actually causes tumor-suppressing genes to be turned off."
In the study, the researchers used "Big data" analyses to reconstruct the RNA thought to form global regulatory networks within breast tumor cells and their matched normal tissues. This approach identified the fact that 3'UTRs are vital in regulating these global regulatory networks. Using this new information, they then disrupted these networks within breast cancer cells to test the effects on tumor growth.
Authors show that knockdown of NUDT21, a master 3′ UTR-shortening regulator, represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Thus, the results suggest a major role of 3′ UTR shortening in repressing tumor-suppressor genes in trans by disrupting competing endogenous RNA crosstalk, rather than inducing proto-oncogenes in cis.