Roles of LIN28 Proteins in Cholangiocarcinoma

Abstract

LIN28 is an RNA-binding protein, a known as regulator of microRNAs biogenesis and play a role in multiple cellular functions such as stem cell maintenance, cell metabolism and implicated in oncogenesis. In cancer study, LIN28 protein is frequently expressed and associated with tumor aggressiveness and poor disease outcome. Previous studies have shown that paralog-LIN28B was upregulated in during CCA development. However, the role of LIN28B in cholangiocarcinogenesis remains largely unknown. The present study, we found LIN28B is overexpressed in CCA patients' tissues. Overexpression of LIN28B in cholangiocytes-MMNK-1 cells showed that LIN28B enhanced cell proliferation, clonogenic potential, and promoted epithelial-to mesenchymal transition (EMT). Moreover, we found LIN28B enhanced cancer stem cells marks, sphere forming ability in MMNK-1 cells. Mechanistically, we found that TGFβI protein which is downstream target of TGF-β signaling was upregulated and migration activity of LIN28B-overexpressing MMNK-1 cells was decreased when inhibit the TGF-β/TGFβI cascade. Collectively, our findings suggest that LIN28B may play a role in generating subpopulation of CCA by exhibiting cancer stem-like properties in cholangiocytes via partly activated of TGF-β signaling. Therefore, LIN28B pathway could become an attractive target for new therapeutic intervention of CCA.