Researchers from USTC discover a Novel Function for p53 in Melanoma

  • [2011-10-20]

    p53 is the most famous tumour suppressor gene, which undergoes a frequently loss-of-function mutations in more than 50% of the human malignant tumours. However, high-level expression of wild-type p53 is often found in melanoma and p53 thus fails to act as an effective tumor suppressor. Moreover,  p53 sometimes even protects melanoma cells from drug treatments. This observation had puzzled researchers in this area for many years.

    The puzzlement, however, will be eliminated partly by the research paper "MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma" which was published on the renowned international multidisciplinary journal Proceedings of the National Academy of Sciences, USA (PNAS) online. The paper was finished by Dr. WU Mian' s Lab at the University of Science and Technology of China (USTC) and Dr. ZHANG Xudong' s Lab at the University of Newcastle (Australia) on Sep. 6, 2011.

    Dr. Wu and Dr. Zhang' s lab discovered that wild-type p53 regulated expression level of a microRNA namely miRNA-149*, which increased stability of an anti-apoptosis protein Mcl-1, and finally made melanoma cells more adaptive to ER stress. The works revealed a p53-dependent, melanoma-specific signalling pathway that contributed to survival of melanoma cells, and this pathway was not common in osteosarcoma, lung and colon cancers. Moreover, significantly high expression level of miRNA-149*, which should be a useful biomarker for melanoma diagnosis, was indeed observed in 60 fresh melanoma isolates. Inhibition assay in mouse model also indicated a possibility that miRNA-149* might be an effective therapeutic target for clinical trails in melanoma.

    The schematic illustration of the proposed model depicting a unique p53-mediated prosurvival pathway in melanoma.(the p53–miR-149*–GSK3α–Mcl-1 signaling pathway in melanoma)/Copyright PNAS

     

    The co-first authors are PhD students JIN Lei and HU Wanglai in Dr. WU Mian 's lab, and JIANG Chenchen in Dr. ZHANG Xudong' s lab.

    This work was supported by the grants from the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Ministry of Science and Technology.

    (Dr. WU Mian' Lab, School of Life Sciences, USTC)

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