P53 target miR-29c-3p suppresses colon cancer cell invasion and migration through inhibition of PHLDB2

Abstract

miR-29c-3p is a potential tumor suppressor microRNA that is reportedly downregulated in several types of human cancers, but its role in colon cancer remains to be elucidated. Meanwhile, TP53, one of the most important tumor suppressors, is highly mutated in colon cancer. In the attempt to connect p53 and miR-29c-3p, we found that the upstream of miR-29c-3p gene contains a functional p53 consensus responsive element that is driven by p53 transcriptional factor activity, suggesting miR-29c-3p as a direct p53 target gene. Through online software prediction and in vivo validation, we demonstrated that Pleckstrin Homology Like Domain Family Member 2 (PHLDB2) is a valid miR-29c-3p target gene. Analysis of human cancer databases available from PROGgeneV2 showed that higher expression of PHLDB2 is associated with shorter overall survival and metastasis-free survival of colon cancer patients. Further, suppression of colon cancer cell invasion and migration by miR-29c-3p was significantly attenuated in the presence of ectopic PHLDB2, indicating PHLDB2 is a critical downstream target of miR-29c-3p. Collectively, our findings present the first to elucidate that miR-29c is a direct p53 target gene, and also identify PHLDB2 as an important miR-29c target gene involved in colon cancer metastasis.