期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 235, 期 3, 页码 2866-2880出版社
WILEY
DOI: 10.1002/jcp.29192
关键词
colon cancer; GATA6; miR-203; stemness
资金
- Ministry of Science and Technology, Taiwan [MOST 101-2320-B-010-071-MY3, MOST104-2320-B-010-007, MOST105-2320-B-010-030]
The interaction between hyaluronan and CD44, an important cancer stem-cell marker, stimulates various tumor cell-specific functions such as the stemness of tumor cells. microRNA-203 (miR-203) can be downregulated by this interaction in human colorectal cancer (CRC) cells, which increases their stemness; however, the underlying mechanism is not yet defined. Here, we show that overexpression and sequestration of miR-203 in HCT-116 and HT-29 human CRC cells reduces and enhances their stemness, respectively. We also show that GATA-binding factor 6 (GATA6) is a direct target of miR-203. Our results indicate that upregulated expression of this transcription factor not only restores the self-renewal abilities of miR-203-overexpressing HCT-116 and HT-29 cells but also promotes the stemness properties of their parental counterparts. More important, we show that silencing the expression of either LRH-1 or Hes-1 is sufficient to diminish the stemness-promoting effects of GATA6 in human CRC cells. Together, our findings delineate the stemness-inhibitory mechanism of miR-203 in human CRC cells and suggest that this miR is a potential therapeutic agent for colorectal cancer.
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