Understanding the mechanism by which cell growth, migration, polyploidy, and tumourigenesis are regulated may provide important therapeutic strategies for cancer therapy. Here we identify the Skp2-macroH2A1 (mH2A1)-CDK8 axis as a critical pathway for these processes, and deregulation of this pathway is associated with human breast cancer progression and patient survival outcome. We showed that mH2A1 is a new substrate of Skp2 SCF complex whose degradation by Skp2 promotes CDK8 gene and protein expression. Strikingly, breast tumour suppression upon Skp2 deficiency can be rescued by mH2A1 knockdown or CDK8 restoration using mouse tumour models. We further show that CDK8 regulates p27 protein expression by facilitating Skp2-mediated p27 ubiquitination and degradation. Our study establishes a critical role of Skp2-mH2A1-CDK8 axis in breast cancer development and targeting this pathway offers a promising strategy for breast cancer therapy.

The newly designed device can remotely control the renal artery, which made clamping and unclamping much easier. It is effective and safe in LPN.

Recurrent ischemic priapism is a problem in clinical treatment. Most of the cases require more invasive surgery to shunt the blood stasis. We introduce a modified technique in treating recurrent ischemic priapism. The technique described is applied to acute ischaemic priapic episodes in patients with a history of stuttering priapism. It was carried out by a Winter's shunt combined with a continuous cavernosal irrigation system. Priapism was effectively resolved on the patients without recurrence. The four patients who received this treatment recovered most sexual function after 6 months follow-up.

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