Spermiogenesis, occurring in the male testis, is a complicated and highly-ordered developmental process resulting in the production of fertile mature sperm. In Gekko japonicus, this process occurs in 7 steps during wh...Spermiogenesis, occurring in the male testis, is a complicated and highly-ordered developmental process resulting in the production of fertile mature sperm. In Gekko japonicus, this process occurs in 7 steps during which the spermatids undergo dramatic changes in the cytoskeleton and nucleus. Here, we cloned and sequenced the cDNA of the mammalian KIFC1 homologue in the testis of G. japonicus. The 2 344 bp full-length cDNA sequence contained a 191 bp 5’-untranslated region, a 134 bp 3’-untranslated region and a 2 019 bp open reading frame encoding a protein of 672 amino acids. Tissue expression analysis revealed the highest expression of kifc1 mRNA was in the testis. Fluorescence in situ hybridization revealed that the kifc1 mRNA signal was hardly detected in step 1 spermatids but became concentrated at the acrosome of step 2 spermatids and abundant in the nucleus of step 5 spermatids where the nucleus then undergoes dramatic elongation and compression. The kifc1 mRNA signal then gradually disappears in mature sperm. This expression of KIFC1 at specific stages of spermiogenesis in G. japonicus implies its important role in the major cytological transformations such as acrosome biogenesis and nucleus morphogenesis.展开更多
Mitotic kinesin KIFC1 plays critical roles in mitosis by regulating the spindle length,pole formation,and known for clustering extra centrosomes in cancer cells.Centrosome clustering is associated with the survival of...Mitotic kinesin KIFC1 plays critical roles in mitosis by regulating the spindle length,pole formation,and known for clustering extra centrosomes in cancer cells.Centrosome clustering is associated with the survival of cancer cells,but this phenomenon remains obscure in prostate cancer(PCa).The present study demonstrated that PCa cells showed centrosome amplification and clustering during interphase and mitosis,respectively.KIFC1 is highly expressed in PCa cells and tumor tissues of prostatic adenocarcinoma(PAC)patients.Up-regulation of KIFC1 facilitated the PCa cell survival in vitro by ensuring bipolar mitosis through clustering the multiple centrosomes,suggesting centrosome clustering could be a leading cause of prostate carcinogenesis.Conversely,the silencing of KIFC1 resulted in normal centrosome number or multipolar mitosis by inhibiting the clustering of amplified centrosomes in PCa cells.Besides,knockdown of KIFC1 by RNAi in PCa cells reduced cancer cell survival,and proliferation.KIFC1 interacted with centrosome structural protein Centrin 2 in clustering of amplified centrosomes in PCa cells to ensure the bipolar mitotic spindle formation.Knockdown of Centrin 2 in PCa cells inhibited the centrosome amplification and clustering.Moreover,up-regulated KIFC1 promotes PCa cell proliferation via progression of cell cycle possibly through aberrant activation of cyclin dependent kinase 1(Cdk1).Therefore,KIFC1 can be a prognostic marker and therapeutic target of PCa for inhibiting the cancer cell proliferation.展开更多
基金supported by the Natural Sciences Foundation of China (31170376)Zhejiang Province Natural Science Foundation of China (LY16C030001 LY18C040005)
文摘Spermiogenesis, occurring in the male testis, is a complicated and highly-ordered developmental process resulting in the production of fertile mature sperm. In Gekko japonicus, this process occurs in 7 steps during which the spermatids undergo dramatic changes in the cytoskeleton and nucleus. Here, we cloned and sequenced the cDNA of the mammalian KIFC1 homologue in the testis of G. japonicus. The 2 344 bp full-length cDNA sequence contained a 191 bp 5’-untranslated region, a 134 bp 3’-untranslated region and a 2 019 bp open reading frame encoding a protein of 672 amino acids. Tissue expression analysis revealed the highest expression of kifc1 mRNA was in the testis. Fluorescence in situ hybridization revealed that the kifc1 mRNA signal was hardly detected in step 1 spermatids but became concentrated at the acrosome of step 2 spermatids and abundant in the nucleus of step 5 spermatids where the nucleus then undergoes dramatic elongation and compression. The kifc1 mRNA signal then gradually disappears in mature sperm. This expression of KIFC1 at specific stages of spermiogenesis in G. japonicus implies its important role in the major cytological transformations such as acrosome biogenesis and nucleus morphogenesis.
基金Natural Science Foundation of Zhejiang Province,China(No.LY20H040010).
文摘Mitotic kinesin KIFC1 plays critical roles in mitosis by regulating the spindle length,pole formation,and known for clustering extra centrosomes in cancer cells.Centrosome clustering is associated with the survival of cancer cells,but this phenomenon remains obscure in prostate cancer(PCa).The present study demonstrated that PCa cells showed centrosome amplification and clustering during interphase and mitosis,respectively.KIFC1 is highly expressed in PCa cells and tumor tissues of prostatic adenocarcinoma(PAC)patients.Up-regulation of KIFC1 facilitated the PCa cell survival in vitro by ensuring bipolar mitosis through clustering the multiple centrosomes,suggesting centrosome clustering could be a leading cause of prostate carcinogenesis.Conversely,the silencing of KIFC1 resulted in normal centrosome number or multipolar mitosis by inhibiting the clustering of amplified centrosomes in PCa cells.Besides,knockdown of KIFC1 by RNAi in PCa cells reduced cancer cell survival,and proliferation.KIFC1 interacted with centrosome structural protein Centrin 2 in clustering of amplified centrosomes in PCa cells to ensure the bipolar mitotic spindle formation.Knockdown of Centrin 2 in PCa cells inhibited the centrosome amplification and clustering.Moreover,up-regulated KIFC1 promotes PCa cell proliferation via progression of cell cycle possibly through aberrant activation of cyclin dependent kinase 1(Cdk1).Therefore,KIFC1 can be a prognostic marker and therapeutic target of PCa for inhibiting the cancer cell proliferation.
