Hsa-miR-520d induces hepatoma cells to form normal liver tissues via a stemness-mediated process.
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 1 month. We are the first to demonstrate the loss of malignant properties in cancer cells in vivo through 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-520d appears to be through the conversion of cancer cells to normal stem cells, maintaining p53 upregulation.
Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, 86 Nishicho, Yonago, Tottori 683-8503, Japan.
Satoshi
S
Tsuno
Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, 86 Nishicho, Yonago, Tottori 683-8503, Japan.
Xinhui
X
Wang
Division of Organ Pathology, Tottori University, 86 Nishicho, Yonago, Tottori 683-8503, Japan.
Kohei
K
Shomori
Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, 86 Nishicho, Yonago, Tottori 683-8503, Japan.
Junichi
J
Hasegawa
Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, 86 Nishicho, Yonago, Tottori 683-8503, Japan.
Norimasa
N
Miura
D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D054337:Cell Dedifferentiation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives / Q000032:analysis; D019175:DNA Methylation / Q000235:genetics; D051959:ELAV Proteins / Q000235:genetics; D000067777:ELAV-Like Protein 2; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008099:Liver / Q000166:cytology; D008113:Liver Neoplasms / Q000235:genetics*; D055432:Metabolomics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D000071317:Nanog Homeobox Protein; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D039904:Pluripotent Stem Cells / Q000166:cytology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D012709:Serum Albumin / Q000096:biosynthesis; D000075462:Serum Albumin, Human; D019098:Telomerase / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
C422455:ALB protein, human; D051959:ELAV Proteins; D000067777:ELAV-Like Protein 2; C086811:ELAVL2 protein, human; D018398:Homeodomain Proteins; C575048:MIRN520 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D012709:Serum Albumin; D016159:Tumor Suppressor Protein p53; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; C509186:TERT protein, human; D019098:Telomerase; D000075462:Serum Albumin, Human