RRC ID 57835
著者 Miura N, Ishihara Y, Miura Y, Kimoto M, Miura K.
タイトル miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives.
ジャーナル BMC Cancer
Abstract BACKGROUND:Human microRNAs (miRNAs) have diverse functions in biology, and play a role in nearly every biological process. Here we report that miR-520d-5p (520d-5p) causes undifferentiated cancer cells to adopt benign or normal status in vivo in immunodeficient mice via demethylation and P53 upregulation. Further we found that 520-5p causes normal cells to elongate cellular lifetime and mesenchymal stem cell-like status with CD105 positivity. We hypothesized that ectopic 520d-5p expression reduced mutations in undifferentiated type of hepatoma (HLF) cells through synergistic modulation of methylation-related enzymatic expression.
METHODS:To examine whether there were any changes in mutation status in cells treated with 520d-5p, we performed next generation sequencing (NGS) in HLF cells and human iPSC-derivative cells in pre-mesenchymal stem cell status. We analyzed the data using both genome-wide and individual gene function approaches.
RESULTS:520d-5p induced a shift towards a wild type or non-malignant phenotype, which was regulated by nucleotide mutations in both HLF cells and iPSCs. Further, 520d-5p reduced mutation levels in both the whole genome and genomic fragment assemblies.
CONCLUSIONS:Cancer cell genomic mutations cannot be repaired in most contexts. However, these findings suggest that applied development of 520d-5p would allow new approaches to cancer research and improve the quality of iPSCs used in regenerative medicine.
巻・号 19(1)
ページ 587
公開日 2019-6-15
DOI 10.1186/s12885-019-5786-y
PII 10.1186/s12885-019-5786-y
PMID 31202279
PMC PMC6570841
MeSH Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / pathology Cell Line, Transformed DNA-Binding Proteins / metabolism Gene Expression Regulation, Neoplastic Humans Induced Pluripotent Stem Cells* / metabolism Liver Neoplasms / genetics* Liver Neoplasms / pathology Mesenchymal Stem Cells / metabolism MicroRNAs / genetics* Mutation
IF 3.15
引用数 2
リソース情報
ヒト・動物細胞 253G1(HPS0002)