title: Adipose tissue-secreted miR-27a promotes liver cancer by targeting FOXO1 in obese individuals.
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.
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Baozhen
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shao
authors.affiliation: Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Suo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Stomatology, Jilin University, Changchun, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
keywords: FOXO1; adipose tissue; miR-27a; obesity; primary liver cancer