The role and mechanism of miR-374 regulating the malignant transformation of mesenchymal stem cells.

The role and mechanism of miR-374 regulating the malignant transformation of mesenchymal stem cells.
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miR-374调控间充质干细胞恶性转化的作用及机制

DOI:
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发表时间:
2018
影响因子:
2.2
通讯作者:
Qian Hui
Qian Hui
中科院分区:
医学4区
文献类型:
--
作者:
Sun Zixuan;Chen Jingyan;Zhang Jiao;Ji Runbi;Xu Wenrong;Zhang Xu;Qian Hui

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MicroRNAs (miRNAs) play important roles in cell transformation and carcinogenesis. We have previously established a tumor cell line K3 transformed from rat bone marrow-derived mesenchymal stem cells (rBM-MSCs). However, the underlying mechanism involved in MSC transformation remains unclear. Herein, we identified the key miRNAs that regulate the transformation of rBM-MSCs, and clarified their biological roles. Microarray and qRT-PCR results showed an increased expression of miR-374 but decreased expressions of miR-199a, miR-145, miR-34a, and miR-214 in K3 cells compared to rBM-MSCs. MiR-374 overexpression in rBM-MSCs increased the colony number and the proportion of the cells in S-phase. In addition, miR-374 overexpression reduced E-cadherin expression and increased N-cadherin expression in rBM-MSCs, promoting the migration ability of these cells. On the contrary, miR-374 knockdown in K3 cells led to impaired proliferation and migration capacities. Furthermore, wnt5a was identified as a target gene of miR-374. MiR-374 overexpression upregulated β-catenin expression in rBM-MSCs while miR-374 knockdown downregulated that in K3 cells. In conclusion, miR-374 promotes the proliferation and migration of transformed MSCs by regulating Wnt5a/β-catenin signaling pathway, which provides evidence for the contribution of miRNA to MSC transformation and suggests a new role of miR-374 in cancer development and progression.
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