Testicular Advantage Ct Expression Protein And Protein Research

Background：Spermatogenesis is a highly complex process of cell division and differentiationwhich is contained spermatogonia self-renew, meiosis and spermiogenesis. Theseprocesses is regulated by several stage express gene in testis. Any disorders of theprocesses will cause arrest of spermatogenesis. It is reported in male infertility casesand gene knockout mouse model. On the other hand, In the testis, the similar featuresof cells in the germ cell differentiation pathway and cancer cells includeimmortalization, which is involved in transformation, induction of meiosis which canlead to aneuploidy, and migration which contributes to metastasis.Interestingly, many of the genes predominantly expressed in the testes are in agroup named cancer/testis (CT) genes, and are ectopically activated in at least onetype of cancer. They often encode antigens that are immunogenic in cancer patients,and present the potential for use as biomarkers and targets for immunotherapy.. Todate, over138CT genes and gene families have been identified by eitherimmunological screening methods or mRNA expression database analysis. Wepropose that testicular proteins are not only involved in spermatogenesis, but also intumor development.Until now, only1500proteins in the human testis have been identified. This is incomparison with the over4000proteins identified in the haploid germ cells and4Cgerm cells of mice. This demonstrates that there is still a limited knowledge of thehuman testis proteome.Methods and results： In this study, using an advanced proteomics platform, we have identified7346unique proteins within the human testis with a high degree of confidence.Immunohistochemistry （IHC） data from the Human Protein Atlas database showsover90%（1833/2020） of identified proteins can be detected in the human testisusing specific antibodies. To make the data widely available to the scientificcommunity, an online Human Testis Proteome Database was built. Many of theidentified human testicular proteins are associated with human infertility, especiallyhuman testicular predominantly expressed proteins （HTPEPs）. Further analysis ofHTPEPs suggested most are ectopically expressed in tumors. We characterized sixnovel cancer/testis genes （TMPRSS12, TPPP2, PRSS55, DMRT1, PIWIL1,HEMGN, C1ORF14）, which map to cancer-associated genetic variants positions, inboth the cancer and testis tissues using genome-wide analyses.Futher analysis of1700012A16riken （homology of human C1ORF14） inmouse reveales that1700012A16riken mainly expressed in testis. And1700012A16riken expression initials in pachytene stage of spermatocyte of14daysold mouse; then enriched in the spindle-like region in the meiotic process; anddispeared in the elongating spermatid.1700012A16riken knockout increasing thearrested cell number of meiotic spermatocyte and decreasing the sperm quantity.1700012A16riken is found to interated with Hspa2, but not effected Hspa2expression.The protein sequence of Shcbp1, Fbxo11and Fbxo10are shown some similarities of 1700012A16riken. Shcbp1, Fbxo11and Fbxo10are expressed in mouse testis and noteffected by1700012A16riken knoctout.4modified positon of1700012A16riken arefound. These position are conservation in many mammal. It is indicated that thesemodifications are inportant in the structure and fuction of1700012A16riken.Conclution：Our results provide a molecular connection between spermatogenesis andtumorigenesis and broaden the range of cancer antigen choice available forimmunotherapy. Further analysis reveals that1700012A16riken is important inspermatogenesis. It also provide a novel mechanism for male subfertility.