Abstract
Fully understanding the mechanism of how Cholangiocarcinoma (CCA) development and discovering promising therapeutic drugs are important to improve patients' survival time. This study identifies that microRNA-455-5p (miR-455-5p) targets protein phosphatase 1 regulatory subunit 12A (PPP1R12A), an effect that represses mitogen-activated protein kinase (MAPK) and PI3K/AKT pathway activation, thereby controlling CCA cells survival and metastasis. Moreover, miR-455-5p expression is reduced in CCA tissues and negative correlation with PPP1R12A and PPP1R12A knockdown phenotypic mimics miR-455-5p' effects on CCA cells. Furthermore, we demonstrate that galangin inhibits CCA growth both in vitro and in vivo, which is associated with increased miR-455-5p and repressed PPP1R12A expression. In support, overexpression of miR-455-5p abrogates those galangin-mediated anti-CCA effects. These findings establish an essential role of miR-455-5p in CCA development and galangin may provide a potential therapeutic adjuvant agent for anti-CCA treatment.