Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
ISSN: 2157-7013
Shihua Wang and Robert Chunhua Zhao
Peking Union Medical College Hospital, China
Scientific Tracks Abstracts: J Cell Sci Ther
The tumorigenicity of human pluripotent stem cells (hPSCs) has been considered to be a major hurdle for their clinical applications. Here, we found that downregulation of miR-302 suppresses the tumorigenicity of hNT-2 cells (a human embryonal carcinoma pluripotent stem cell line). By gain- and loss-of-function approaches, we demonstrated that miR-302 promotes the proliferation and tumorigenicity of hPSCs through the dominant regulation of a set of cell cycle inhibitors and subsequent acceleration of the G1 to S transition. Importantly, we also found that downregulation of miR-302 damages the self-renewal and pluripotency, and promotes differentiation of hPSCs. The underlying mechanism is that high endogeneous expression of miR-302 suppresses the expression of Akt1 by directly targeting its 3'UTR, and subsequently maintains pluripotent factor OCT4 at high level in hPSCs. However, overexpression of miR-302 in human mesenchymal stem/stromal cells (hMSCs) dose not leads to tumor formation in vitro or in vivo. These findings indicated that in human pluripotent stem cells miR-302 is not a causal factor, but just a contributing factor for the tumorigenicity through promoting G1 to S transition and maintaining OCT4 at high level by directly inhibiting AKT1.
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