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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma
Oncogene, Volume 32, No. 26, Year 2013
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Description
WEE1 kinase has been described as a major gate keeper at the G2 cell cycle checkpoint and to be involved in tumour progression in different malignant tumours. Here we analysed the expression levels of WEE1 in a series of melanoma patient samples and melanoma cell lines using immunoblotting, quantitative real-time PCR and immunohistochemistry. WEE1 expression was significantly downregulated in patient samples of metastatic origin as compared with primary melanomas and in melanoma cell lines of high aggressiveness as compared with cell lines of low aggressiveness. Moreover, there was an inverse correlation between the expression of WEE1 and WEE1-targeting microRNA miR-195. Further analyses showed that transfection of melanoma cell lines with miR-195 indeed reduced WEE1 mRNA and protein expression in these cells. Reporter gene analysis confirmed direct targeting of the WEE1 3′ untranslated region (3′UTR) by miR-195. Overexpression of miR-195 in SK-Mel-28 melanoma cells was accompanied by WEE1 reduction and significantly reduced stress-induced G2-M cell cycle arrest, which could be restored by stable overexpression of WEE1. Moreover, miR-195 overexpression and WEE1 knockdown, respectively, increased melanoma cell proliferation. miR-195 overexpression also enhanced migration and invasiveness of melanoma cells. Taken together, the present study shows that WEE1 expression in malignant melanoma is directly regulated by miR-195. miR-195-mediated downregulation of WEE1 in metastatic lesions may help to overcome cell cycle arrest under stress conditions in the local tissue microenvironment to allow unrestricted growth of tumour cells. © 2013 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Bhattacharya, Animesh
Germany, Leipzig
Universität Leipzig
Schmitz, Ulf
Germany, Rostock
Universität Rostock
Wolkenhauer, Olaf
Germany, Rostock
Universität Rostock
Kunz, Manfred
Germany, Leipzig
Universität Leipzig
Statistics
Citations: 82
Authors: 4
Affiliations: 2
Identifiers
Doi:
10.1038/onc.2012.324
ISSN:
14765594
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Study Approach
Quantitative