miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway

miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway

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Proliferation, a key feature of cancer cells, accounts for the majority of cancer-related diseases resulting in mortality.MicroRNAs here (miRNAs) plays important post-transcriptional modulation roles by acting on multiple signaling pathways, but the underlying mechanism in proliferation and tumorigenicity is unclear.Here, we identified the role of miR-150 in proliferation and tumorigenicity in leukemia stem cells (LSCs) (CD34+CD38- cells).miR-150 expression was significantly down-regulated in LSCs from leukemia cell lines and clinical samples.

Functional assays demonstrated that increased miR-150 expression inhibited proliferation and clonal and clonogenic growth, enhanced chemosensitivity, and attenuated tumorigenic activity of LSCs in vitro.Transplantation animal studies revealed that miR-150 overexpression progressively abrogates tumour growth.Immunohistochemistry assays demonstrated that miR-150 overexpression enhanced caspase-3 level and reduced Ki-67 level.Moreover, luciferase reporter assays indicated Nanog is a direct and functional target click here of miR-150.

Nanog silencing using small interfering RNA recapitulated anti-proliferation and tumorigenicity inhibition effects.Furthermore, miR-150 directly down-regulated the expression of other cancer stem cell factors including Notch2 and CTNNB1.These results provide insights into the specific biological behaviour of miR-150 in regulating LSC proliferation and tumorigenicity.Targeting this miR-150/Nanog axis would be a helpful therapeutic strategy to treat acute myeloid leukemia.