BACKGROUND: The search for Ca²⁺ channels residing in sperm has led to the recent cloning and characterization of a novel gene, named CatSper, which codes for a unique Ca²⁺ channel expressed exclusively in the testis. It plays an essential role in sperm motility, penetration into the oocyte, and ultimately in male fertility. In this study, we assessed the temporal profile of CatSper gene expression during mouse testis development and performed a semi‐quantitative evaluation of expression levels in a group of subfertile men which lack sperm motility. METHODS: A small piece of testicular tissue obtained by either multi‐site testicular biopsy or orchidectomy was used for semi‐quantitative RT–PCR of CatSper and β2‐microglobulin (β2m, as an internal control) genes. RESULTS: Our results reveal that: (i) the expression of mouse CatSper is developmentally regulated with a direct correlation between CatSper expression and mouse sexual maturation. CatSper gene expression is first detected at 3 weeks of age and coincides with the appearance of round spermatids in the developing mouse testis. (ii) There is a significant reduction in the level of CatSper gene expression (up to 3.5‐fold difference) among patients which lack sperm motility as compared with patients whose infertility cannot be ascribed to a deficiency in motility (used as a control). CONCLUSIONS: The data obtained in this study support a potential role for CatSper in sperm motility and fertility in mouse and human. CatSper is therefore implicated as a potential target to explore the molecular mechanisms of male infertility.

The RNA-binding protein Musashi1 (MSI1) is a marker of progenitor cells in the nervous system functioning as a translational repressor. We detected MSI1 mRNA in several bladder carcinoma cell lines, but not in cultured normal uroepithelial cells, whereas the paralogous MSI2 gene was broadly expressed. Knockdown of MSI1 expression by siRNA induced apoptosis and a severe decline in cell numbers in 5637 bladder carcinoma cells. Microarray analysis of gene expression changes after MSI1 knockdown significantly up-regulated 735 genes, but down-regulated only 31. Up-regulated mRNAs contained a highly significantly greater number and density of Musashi binding sites. Therefore, a much larger set of mRNAs may be regulated by Musashi1, which may affect not only their translation, but also their turnover. The study confirmed p21(CIP1) and Numb proteins as targets of Musashi1, suggesting additionally p27(KIP1) in cell-cycle regulation and Jagged-1 in Notch signalling. A significant number of up-regulated genes encoded components of stress granules (SGs), an organelle involved in translational regulation and mRNA turnover, and impacting on apoptosis. Accordingly, heat shock induced SG formation was augmented by Musashi1 down-regulation. Our data show that ectopic MSI1 expression may contribute to tumorigenesis in selected bladder cancers through multiple mechanisms and reveal a previously unrecognized function of Musashi1 in the regulation of SG formation.

Objectives:  The Nucleostemin (NS) gene encodes a nucleolar protein enriched in adult and embryonic stem cells. NS is thought to regulate cancer cell proliferation, but the mechanisms involved are poorly understood. In this study, we have investigated the role of NS in bladder cancer.Materials and methods:  Expression of NS was determined by quantitative reverse transcription–polymerase chain reaction in bladder carcinoma cell lines and in normal uro‐epithelial cell cultures. We used an RNAi strategy to investigate the function of NS in two selected carcinoma cell lines.Results:  High NS expression was found in most bladder carcinoma cell lines and normal uro‐epithelial cells. Knockdown of NS expression induced a severe decline in cell proliferation in 5637 and SW1710 cell lines, both with mutant p53. Apoptosis was more strongly enhanced in 5637 cells lacking RB1 than in SW1710 cells lacking p16^INK4A. Moreover, NS‐siRNA‐treated 5637 cells accumulated mainly in G₂/M, whereas SW1710 cells arrested in G₀/G₁.Conclusion:  Our data indicate that NS expression is necessary for cell proliferation and evasion of apoptosis in bladder cancer cells, independent of its effect on p53. Also, we speculate that the precise effect of NS on cell cycle regulation may relate to functional status of RB1 and CDKN2A/p16^INK4A.

Aim: To evaluate PlncRNA-1, TUG1 and FAM83H-AS1 gene expression and their possible role as a biomarker in gastric cancer (GC) progression. Patients & methods: Long noncoding RNA expressions and clinicopathological characteristics were assessed in 70 paired GC tissues. Furthermore, corresponding data from 318 GC patients were downloaded from The Cancer Genome Atlas database. Results: Expression of PlncRNA-1 and TUG1 were significantly upregulated in GC tumoral tissues, and significantly correlated with clinicopathological characters. However, FAM83H-AS1 showed no consistently differential expression. The expression of these three long noncoding RNAs was significantly higher in The Cancer Genome Atlas tumoral tissues. Conclusion: In conclusion, PlncRNA-1 and TUG1 genes may play a critical role in GC progression and may serve as potential diagnostic biomarkers in GC patients.