MiR-155 Overexpression Promotes Genomic Instability by Reducing High-fidelity Polymerase Delta Expression and Activating Error-Prone DSB Repair.

ABSTRACT:

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miR-155 is an oncogenic miRNA that is often overexpressed in cancer and is associated with poor prognosis. miR-155 can target several DNA repair factors, including RAD51, MLH1, and MSH6, and its overexpression results in an increased mutation frequency in vitro, although the mechanism has yet to be fully understood. Here, we demonstrate that overexpression of miR-155 drives an increased mutation frequency both in vitro and in vivo, promoting genomic instability by affecting multiple DNA repair pathways. miR-155 overexpression causes a decrease in homologous recombination, but yields a concurrent increase in the error-prone nonhomologous end-joining pathway. Despite repressing established targets MLH1 and MSH6, the identified mutation pattern upon miR-155 overexpression d

SUBMITTER: Czochor JR 

PROVIDER: S-EPMC5021065 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature