Conversion of Human Hepatoma Cells by 520d-5p to Benign or Normal Liver Tissues via a stemness-Mediated Process

¹Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, 86 Nishicho, Yonago, Tottori 683-8503, Japan
²Division of Organ Pathology, Tottori University, 86 Nishicho, Yonago, Tottori 683-8503, Japan
³PEZY-Pharma, Inc., 2-13-14 Hatagasaki, Yonago, Tottori 683-0845, Japan

*Correspondence author: Norimasa Miura, Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, 86 Nishicho, Yonago, Tottori 683-8503, Japan, E-mail: [email protected]
Received: February 28, 2019
Published: September 17, 2020

ABSTRACT

The human ncRNA gene RGM249 regulates the extent of differentiation of cancer cells and the conversion of 293FT cells to hiPSCs. To identify the factors underlying this process, we investigated the effects of lentivirally inducing miR-520d expression in 293FT and HLF cells in vitro. Subsequently, we evaluated tumor formation in a xenograft model. Transformed HLF cells were Oct4 and Nanog positive within 24 h, showed p53 upregulation and hTERT downregulation, and mostly lost their migration abilities. After lentiviral infection, the cells were intraperitoneally injected into mice, resulting in benign teratomas (6%), the absence of tumors (87%) or differentiation into benign liver tissues (7%) at the injection site after one month. We are the first to demonstrate the loss of malignant properties in cancer cellsin vivothrough the expression of a single microRNA (miRNA). This miRNA successfully converted 293FT and hepatoma cells to hiPSC-like cells. The regulation of malignancy by miR-520dappears to be throughthe conversion of cancer cells to normal stem cells.

 Keywords: Cancer, Stemness, miRNA, Differentiation, iPSC