adipose tissue-secreted mir-27a promotes liver cancer by targeting foxo1 in obese individuals

Baozhen Sun,1,* Jing Li,2,* Dan Shao,2 Yue Pan,2 Yujing Chen,2 Suo Li,1 Xiaoxiao Yao,1 Hang Li,1 Weiwei Liu,3 Ming Zhang,2 Xuewen Zhang,1 Li Chen2 1Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People’s Republic of China; 3School of Stomatology, Jilin University, Changchun, People’s Republic of China *These authors contributed equally to this work Abstract: The current notion that obesity is a major risk factor for the development of and the mortality associated with a subset of liver cancer is well appreciated. However, detailed mechanistic insights underlying this relationship are lacking. Better understanding of the adipose tissue-secreted miRNAs that play a potential role in defining primary liver cancer development and mediating the obesity-cancer communication offers the potential for new insights into tumor growth and interventions to modulate tumor formation and progression. In this study, we clearly demonstrated that miR-27a is more highly upregulated in cancer, plasma, and adipose samples from obese liver cancer cases, and therefore reasoned that miR-27a excreted from adipose tissue leads to liver cancer development. To address this idea, we prepared miR-27a-overexpressing 3T3-L1 adipocytes and cocultured them with HepG2 liver cancer cells. Our results demonstrated that secretory miR-27a promoted liver cancer cell proliferation through the downregulation of the transcription factor FOXO1 and promoted the G1/S cell cycle transition by decreasing the cell cycle inhibitors p21 and p27 and increasing the cell cycle regulator cyclin D1. These findings improve our understanding of the involvement of miR-27a in obesity-liver cancer communication and might provide a novel putative target for obesity-driven primary liver cancer diagnosis and therapy. Keywords: miR-27a, primary liver cancer, obesity, adipose tissue, FOXO1