Cancer/Testis genes in relation to sperm biology and function.
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ABSTRACT:
SUBMITTER: Babatunde KA
PROVIDER: S-EPMC5651463 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
Cancer/Testis genes in relation to sperm biology and function.
Babatunde Kehinde Adebayo KA Najafi Ali A Salehipour Pouya P Modarressi Mohammad Hossein MH Mobasheri Maryam Beigom MB
Iranian journal of basic medical sciences 20170901 9
Cancer testis antigens (CTAs), a large family of tumor-associated and immunogenic antigens expressed in human tumors of various histological origins, are highly restricted to the testis and trophoblast. CTAs have been identified as potent targets for tumor-specific immunotherapeutic advances and have immensely lead to the development of different clinical trials of CTA-based vaccine therapy because of their resilient <i>in vivo</i> immunogenicity and tumor-restricted expression pattern. Bladder ...[more]
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Project description:Tumour-specific antigens have been an area of interest in cancer therapy since their discovery in the middle of the 20th century. In the era of immune-based cancer therapeutics, redirecting our immune cells to target these tumour-specific antigens has become even more relevant. Cancer-testis antigens (CTAs) are a class of antigens with an expression specific to the testis and cancer cells. CTAs have also been demonstrated to be expressed in a wide variety of cancers. Due to their frequency and specificity of expression in a multitude of cancers, CTAs have been particularly attractive as cancer-specific therapeutic targets. There is now a rapid expansion of CTAs being identified and many studies have been conducted to correlate CTA expression with cancer and therapy-resistant phenotypes. Furthermore, there is an increasing number of clinical trials involving using some of these CTAs as molecular targets in pharmacological and immune-targeted therapeutics for various cancers. This review will summarise the current knowledge of the biology of known CTAs in tumorigenesis and the regulation of CTA genes. CTAs as molecular targets and the therapeutic implications of these CTA-targeted anticancer strategies will also be discussed.
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Project description:BackgroundSperm hyperactive motility has previously been shown to influence litter size in pigs, but little is known about the underlying biological mechanisms. The aim of this study was to use RNA sequencing to investigate gene expression differences in testis tissue from Landrace and Duroc boars with high and low levels of sperm hyperactive motility. Boars with divergent phenotypes were selected based on their sperm hyperactivity values at the day of ejaculation (day 0) (contrasts (i) and (ii) for Landrace and Duroc, respectively) and on their change in hyperactivity between day 0 and after 96 h liquid storage at 18 °C (contrast (iii)).ResultsRNA sequencing was used to measure gene expression in testis. In Landrace boars, 3219 genes were differentially expressed for contrast (i), whereas 102 genes were differentially expressed for contrast (iii). Forty-one differentially expressed genes were identified in both contrasts, suggesting a functional role of these genes in hyperactivity regardless of storage. Zinc finger DNLZ was the most up-regulated gene in contrasts (i) and (iii), whereas the most significant differentially expressed gene for the two contrasts were ADP ribosylation factor ARFGAP1 and solute carrier SLC40A1, respectively. For Duroc (contrast (ii)), the clustering of boars based on their gene expression data did not reflect their difference in sperm hyperactivity phenotypes. No results were therefore obtained for this breed. A case-control analysis of variants identified in the Landrace RNA sequencing data showed that SNPs in NEU3, CHRDL2 and HMCN1 might be important for sperm hyperactivity.ConclusionsDifferentially expressed genes were identified in Landrace boars with high and low levels of sperm hyperactivity at the day of ejaculate collection and high and low change in hyperactivity after 96 h of sperm storage. The results point towards important candidate genes, biochemical pathways and sequence variants underlying sperm hyperactivity in pigs.
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