Differential regulation of H3S10 phosphorylation, mitosis progression and cell fate by Aurora Kinase B and C in mouse preimplantation embryos

Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.

Idiopathic teratozoospermia is not correlated with c.144delC polymorphism in the AURKC gene in Sichuan / 中华男科学杂志

Objective@#To investigate the association of a very common mutation of c.144delC in the aurora kinase C (AURKC) gene with idiopathic teratozoospermia in Chinese infertile men in Sichuan.@*METHODS@#Using polymerase chain reaction (PCR) and next-generation sequencing, we analyzed the correlation between c.144delC polymorphism of the AURKC gene and male infertility in 98 idiopathic teratozoospermia patients in comparison with 162 normal fertile men.@*RESULTS@#Neither c.144delC mutation nor other meaningful mutations were detected in the AURKC gene in the 98 idiopathic teratozoospermia patients or the 162 normal controls.@*CONCLUSIONS@#Teratozoospermia is not correlated with c.144delC mutation in the AURKC gene in the men of the Sichuan area. Therefore, large-scale genotyping of the AURKC gene may not be necessary clinically among Chinese patients with idiopathic teratozoospermia.

Genetic genes associated with oligospermia, asthenospermia and teratospermia: Advances in studies / 中华男科学杂志

Approximately 2,300 genes are found to be associated with spermiogenesis and their expressions play important roles in the regulation of spermiogenesis. In recent years, more and more attention has been focused on the studies of the genes associated with oligospermia, asthenospermia and teratospermia and their molecular mechanisms. Some genes, such as GSTM1, DNMT3L, and CYP1A1, have been shown to be potentially associated with oligospermia; some, such as CATSPER1, CRISP2, SEPT4, TCTE3, TEKT4, and DNAH1, with asthenospermia; and still others, such as DPY19L2 and AURKC, with teratospermia. These findings have provided a molecular basis for the studies of the pathogenesis of oligospermia, asthenospermia and teratospermia, as well as a new approach to the exploration of new diagnostic and therapeutic techniques.

Prognostic implications of the phosphatidylinositol 3-kinase/Akt signaling pathway in oral squamous cell carcinoma: overexpression of p-mTOR indicates an adverse prognosis

Background: The development of oral cavity cancer is related to the accumulation of genetic alterations. The activation of AKT is associated with the proliferation and progression of many malignancies. It is thought that MAP kinases, together with the PI3K/AKT/mTOR signaling pathway, promote uncoordinated proliferation via inhibition of PTEN, thus increasing cell survival and mediating cancer progression. However, there are few studies regarding the expression of these proteins in oral squamous cell carcinoma (SCC). Methods: The expression of PI3K, p-mTOR, p-AKT, p-MAPK, and PTEN in 125 oral SCCs, including gingival, palate hard, and alveolar ridge tumors, was examined by immunohistochemistry and correlated with clinicopathological data and survival rates. Results: We observed PI3K, p-mTOR, p-MAPK, p-AKT, and PTEN positive staining in the cytoplasm of most SCC (92.4%, 88.2%, 88.3%, 94.2%, and 25%, respectively). Positive nuclear staining was observed for p-mTOR, PTEN, p-AKT, and p-MAPK (42.9%, 72%, 64.2%, and 58.2%, respectively). Only p-mTOR protein expression was observed on the cell membrane and was present in 44.5% of cases. A statistically significant correlation was found between p-MAPK expression and SCC clinicopathological stages III and IV (p = 0.0042). Lower rates of disease-free survival were found in patients with SCC III / IV (p = 0.001). Patients with positive nuclear staining of p-mTOR displayed a significant increase in disease-free survival rates. Discussion: The identification of prognostic and predictive markers is clinically important because oral cancer is a group of heterogeneous diseases with various biological and clinical characteristics. Conclusion: Our findings suggest that the PI3K/AKT pathway is activated in gingival, hard palate, and alveolar ridge SCCs. We have demonstrated that p-mTOR expression can function as a biomarker for survival in oral SCCs and could be a promising therapeutic target in oral SCC treatment (AU)