A miRNA-mediated attenuation of hepatocarcinogenesis in both hepatocytes and Kupffer cells

Yan Tian; Mingfeng Zhang; Mingjie Fan; Haixia Xu; Shunquan Wu; Sailan Zou; Yangmeng Wang; Dongmei Tang; Chunyan Zhang; Weidong Han; Hua Yu; Xianghui Fu; Wendong Huang

doi:10.1016/j.omtn.2022.08.036

A miRNA-mediated attenuation of hepatocarcinogenesis in both hepatocytes and Kupffer cells

Mol Ther Nucleic Acids. 2022 Aug 28:30:1-12. doi: 10.1016/j.omtn.2022.08.036. eCollection 2022 Dec 13.

Authors

Yan Tian^{1

2}, Mingfeng Zhang², Mingjie Fan², Haixia Xu¹, Shunquan Wu², Sailan Zou¹, Yangmeng Wang², Dongmei Tang¹, Chunyan Zhang³, Weidong Han^{2

4}, Hua Yu^{3

5}, Xianghui Fu^{1

2}, Wendong Huang^{2

5}

Affiliations

¹ Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, China.
² Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA.
³ Department of Immuno-oncology, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA.
⁴ Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang 310016, China.
⁵ Graduate School of Biological Science, City of Hope National Medical Center, Duarte, CA 91010, USA.

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate a variety of physiological and pathological functions. miR-26a is one of the many miRNAs that have been identified as regulators of cancer development and as potential anticancer drug targets. However, the specific cellular and molecular mechanisms by which miR-26a attenuates hepatocarcinogenesis are still elusive. Here, we interrogated mouse models with miR-26a cell-specific overexpression in either hepatocytes or myeloid cells to show that miR-26a strongly attenuated the chemical-induced hepatocellular carcinoma (HCC). miR-26a overexpression broadly inhibited the inflammatory response in both hepatocytes and macrophages by decreasing several key oncogenic signaling pathways in HCC promotion. These findings thus reveal new insights into a concerted role of miR-26a in both hepatocytes and Kupffer cells to suppress hepatocarcinogenesis, thereby highlighting the potential use of miR-26a mimetics as potential approaches for the prevention and treatment of HCC.