Hsa-miR-520d induces hepatoma cells to form normal liver tissues via a stemness-mediated process.
Hsa-miR-520d induces hepatoma cells to form normal liver tissues via a stemness-mediated process.
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DOI：
10.1038/srep03852
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发表时间：
2014-01-24
影响因子：
4.6
通讯作者：
Miura N
中科院分区：
文献类型：
--
作者：
Tsuno S;Wang X;Shomori K;Hasegawa J;Miura N
人ncRNA基因RGM 249调节癌细胞的分化程度和293 FT细胞向hiPSC的转化。为了确定这一过程的潜在因素，我们研究了慢病毒诱导miR-520 d在293 FT和HLF细胞中表达的影响。随后，我们评估了异种移植模型中的肿瘤形成。转化后的HLF细胞在24 h内呈Oct 4和Nanog阳性，p53表达上调，hTERT表达下调，且大多数细胞丧失迁移能力。 在慢病毒感染后，将细胞腹膜内注射到小鼠中，1个月后在注射部位产生良性畸胎瘤（6%）、没有肿瘤（87%）或分化成良性肝组织（7%）。我们是第一个证明通过表达单个microRNA（miRNA）在体内癌细胞中丧失恶性特性的人。该miRNA成功地将293 FT和肝癌细胞转化为hiPSC样细胞。miR-520 d对恶性肿瘤的调节似乎是通过将癌细胞转化为正常干细胞，维持p53上调。
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.
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影响因子：
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