Loss of functionality of the production of microRNAs in tumorigenesis
March 18th, 2010
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The gene TARBP2 (TAR-RNA binding protein 2) is key to the production machinery of microRNA. These microRNAs are short strands of ribonucleic acid that regulate the intensity of the activity of other genes activated and deactivated, and active oncosupresora has been demonstrated in the past. In this study, conducted by a group of scientists from Finland, Portugal, USA and Spain, led by Manel Esteller, who led the group in the Cancer Epigenetics CNIO in Madrid and currently leads the Epigenetics of IDIBELL in Barcelona, have examined a number of cell lines of colorectal cancer, endometrial and gastric cancer for mutations in eight members of the microRNA processing machinery, including RNAasa III family of double-stranded (DICER1and Drosha) and binding proteins RNA, which act as catalytic partners (such as TRBP, an integral component of the complex with DICER1).
In this study we have identified gene mutations that cause a decrease TARBP2 of TRBP protein expression and a defect in the processing of microRNA. A series of experiments revealed that the TARBP2 gene was mutated in 26% (72 cases of the 282 samples) of human tumors analyzed. These mutations have been found in both sporadic and hereditary carcinomas that are characterized by a defect in the repair of small errors in DNA and its progression is due to the ease to produce mutations. Moreover, the reintroduction of the TRBP gene restores the production of microRNAs and inhibits tumor growth. It should be noted also that TRBP dysfunction is associated with a destabilization of the protein DICER1. Taken together, these results explain that during tumorigenesis there is a loss of function of regulating the processing machinery of the microRNA.
In this study we have identified gene mutations that cause a decrease TARBP2 of TRBP protein expression and a defect in the processing of microRNA. A series of experiments revealed that the TARBP2 gene was mutated in 26% (72 cases of the 282 samples) of human tumors analyzed. These mutations have been found in both sporadic and hereditary carcinomas that are characterized by a defect in the repair of small errors in DNA and its progression is due to the ease to produce mutations. Moreover, the reintroduction of the TRBP gene restores the production of microRNAs and inhibits tumor growth. It should be noted also that TRBP dysfunction is associated with a destabilization of the protein DICER1. Taken together, these results explain that during tumorigenesis there is a loss of function of regulating the processing machinery of the microRNA.
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