Increased activity of the epigenetic modifier EZH2 has been associated with different cancers. However, evidence for a functional role of EZH2 in tumorigenesis in vivo remains poor, in particular in metastasizing solid cancers. Here we reveal central roles of EZH2 in promoting growth and metastasis of cutaneous melanoma. In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical EZH2 inhibitor GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology. Comparably, in human melanoma cells, EZH2 inactivation impairs proliferation and invasiveness, accompanied by re-expression of tumour suppressors connected to increased patient survival. These EZH2 target genes suppress either melanoma growth or metastasis in vivo, revealing the dual function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic repression is highly relevant especially during advanced melanoma progression, which makes EZH2 a promising target for novel melanoma therapies.
Diallel mating designs provide to breeders useful genetic information, such as general combining ability (GCA) and specific combining ability (SCA), to help them devise appropriate breeding and selection strategies. Here we report a much‐improved version of DIALLEL‐SAS that was originally released in 1997. The new program, DIALLEL–SAS05, has a clear and user‐friendly interface that was designed to meet users’ needs for various diallel‐cross design experiments. DIALLEL‐SAS05 has major advantages over DIALLEL‐SAS in that: (i) it analyzes not only all four Griffing's diallel methods (both fixed and random models), but it also computes Gardner–Eberhart's Analyses II and III; (ii) it provides desired results from diallel experiments with parent number from 4 to 12, (iii) it can analyze diallel data from any number of environments, and (iv) for a random‐effects model, it provides estimates of GCA (σ2g) and SCA (σ2s) variances, which can be used to estimate additive (σ2A) and dominance (σ2D) variances, and ultimately narrow‐sense heritability (h2). DIALLEL‐SAS05 also provides information on GCA × ENV, SCA × ENV, reciprocal × ENV, maternal × ENV, and nonmaternal × ENV interactions, when applicable. DIALLEL‐SAS05 should greatly improve researchers’ efficiency in analyzing and interpreting diallel‐cross data. The program code is available on a CD from the corresponding author.
• Machine-based analysis of MR radiomics outperformed in TZ cancer against PI-RADS. • Adding MR radiomics significantly improved the performance of PI-RADS. • DKI-derived Dapp and Kapp were two strong markers for the diagnosis of PCa.
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