期刊
CANCERS
卷 10, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/cancers10110443
关键词
Merkel cell carcinoma; Merkel cell polyomavirus; miR-375; LDHB; cell growth
类别
资金
- Swedish Cancer Society
- Cancer Research Funds of Radiumhemmet
- Stockholm County Council
- National Natural Science Foundation of China [81773002]
- Natural Science Foundation of Tianjin [16JCYBJC42400]
- Karolinska Institutet PhD program (KID)
- Karolinska Institutet
MicroRNA-375 (miR-375) is deregulated in multiple tumor types and regulates important targets involved in tumorigenesis and metastasis. This miRNA is highly expressed in Merkel cell carcinoma (MCC) compared to normal skin and other non-MCC skin cancers, and its expression is high in Merkel cell polyomavirus (MCPyV)-positive (MCPyV+) and low in MCPyV-negative (MCPyV-) MCC tumors. In this study, we characterized the function and target of miR-375 in MCPyV+ and MCPyV- MCC cell lines. Ectopic expression of miR-375 in MCPyV- MCC cells resulted in decreased cell proliferation and migration, as well as increased cell apoptosis and cell cycle arrest. However, in MCPyV+ MCC cells, inhibition of miR-375 expression reduced cell growth and induced apoptosis. Additionally, the expression of lactate dehydrogenase B (LDHB), a known target of miR-375, was inversely correlated with miR-375. Silencing of LDHB reduced cell growth in MCPyV- cell lines, while its silencing in MCPyV+ cell lines rescued the cell growth effect mediated by miR-375 inhibition. Together, our results suggest dual roles of miR-375 and LDHB in MCPyV and non-MCPyV-associated MCCs. We propose that LDHB could be a therapeutic target in MCC and different strategies should be applied in virus- and non-virus-associated MCCs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据