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BRAF pseudogene induces cancer

The in vivo role of many pseudogenes remains largely unexplored, especially in cancer. Pier Paolo Pandolfi and colleagues show that overexpression of the Braf pseudogene Braf-rs1 in mice causes the development of an aggressive malignancy similar to human diffuse large B cell lymphoma (Cell doi:10.1016/j.cell.2015.02.043; 2 April 2015). Their data suggest that the oncogenic potential of both Braf-rs1 and its human ortholog, BRAFP1, is based on the function of their transcripts as competitive endogenous RNAs (ceRNAs). Indeed, BRAFP1 seems to function as a sponge, sequestering microRNAs that target BRAF. As a consequence of elevated BRAFP1 levels, BRAF is also upregulated, leading to the activation of MAPK signaling and increased cell proliferation. Importantly, BRAFP1 is often altered in several human cancer types on a genomic or transcriptional level. This work provides an interesting example of a pseudogene involved in disease progression and proposes a ceRNA-mediated mechanism that underpins cancer development.

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Faial, T. BRAF pseudogene induces cancer. Nat Genet 47, 429 (2015). https://doi.org/10.1038/ng.3295

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