The Functional Role Of Mutant P53Gain Of Function In Tumorigenesis

p53is a major tumor suppressor whose function is pivotal for protection against cancer. In over half of human cancers, p53is inactivated due to either point mutation or loss of p53gene. It has been well established that in addition to abrogating the tumor suppressive function of wild-type p53, mutant p53gains new functions and actively contributes to various stages of tumor progression. However, little is known about whether microRNA (miRNA) is involved in the gain-of-function of mutant p53. Here we report miR-27a as a novel downstream transcriptional target of mutant p53-273H. Mutant p53binds to the miR-27a promoter region and suppresses its expression. We also identify epidermal growth factor receptor (EGFR) as a direct target of miR-27a. Via the miR-27a/EGFR axis, mutant p53-273H promotes EGF-induced sustained ERK1/2activation, thereby facilitating cell proliferation and tumorigenesis. Collectively, this work reveals a direct link between the gain-of-function of mutant p53and microRNA, and uncovers a novel mutant p53-273H/miR-27a/EGFR pathway that plays an important role in promoting tumor development.