BACKGROUND: We conducted multiple microarray datasets analyses from clinical and xenograft tumor tissues to search for disease progression-driving oncogenes in prostate cancer (PCa). Sperm-associated antigen 5 (SPAG5) attracted our attention. SPAG5
yle='font-weight:700;'>SPAG5 was recently identified as an oncogene participating in lung cancer and cervical cancer progression. However, the roles of SPAG5 in PCa progression remain unknown. METHODS: SPAG5 expression level in clinical primary PCa, metastatic PCa, castration resistant PCa, neuroendocrine PCa, and normal prostate tissues was investigated. We established multiple in vivo xenografts models using patient-derived tissues and investigated SPAG5 expression trend in these models. We also investigated the functions of SPAG5 in vivo and in vitro studies. Luciferase reporter assays were performed to investigate potential miRNAs that can regulate SPAG5. RESULTS: We identified that SPAG5 expression was gradually increased in PCa progression and its level was significantly associated with lymph node metastasis, clinical stage, Gleason score, and biochemical recurrence. Our results indicated that SPAG5 knockdown can drastically inhibit PCa cell proliferation, migration, and invasion in vitro and supress tumor growth and metastasis in vivo. We identified that miR-539 can directly target SPAG5. Ectopic overexpression of miR-539 can drastically inhibit SPAG5 expression and the restoration of SPAG5 expression can reverse the inhibitory effects of miR-539 on PCa cell proliferation and metastasis. CONCLUSION: Our results collectively showed a progression-driving role of SPAG5 in PCa which can be regulated by miR-539, suggesting that miR-539/SPAG5 can serve as a potential therapeutic target for PCa.
Li Y, etal., Cell Death Discov. 2022 Jul 19;8(1):326. doi: 10.1038/s41420-022-01120-3.
Regulation of alternative splicing (AS) by the splicing factor 3b (SF3B) family plays an essential role in cancer. However, the biological function of SF3B family members in cervical cancer (CC) needs to be further elucidated. In this study, we found that splicing factor 3b subunit 4 (SF3B4) was hig
hly expressed in CC by bioinformatics analysis using cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) data from The Cancer Genome Atlas (TCGA). Then, we demonstrated that high expression of SF3B4 promoted proliferation and invasion abilities of CC cells in vitro and in vivo and that reduced expression of SF3B4 performed the opposite effect. Further RNA-seq and AS analysis showed that sperm-associated antigen 5 (SPAG5) was a downstream target gene of SF3B4. Interestingly, SPAG5 expression was decreased after SF3B4 knockdown because of retained introns (RIs) and reduced maturation of SPAG5 pre-mRNA. Importantly, SPAG5 deficiency impaired the oncogenic effects of SF3B4 overexpression on CC cells. In conclusion, SF3B4 promotes CC progression by regulating the effective splicing of SPAG5. SF3B4 could be a promising target for CC.
Shao X, etal., Mol Reprod Dev 2001 Aug;59(4):410-6.
Outer dense fibers (ODF) and the fibrous sheath (FS) are major cytoskeletal structures in the mammalian sperm tail. The molecular mechanisms underlying their morphogenesis along the axoneme or their function are poorly understood. Recently, we reported the cloning and characterization of Odf2, a maj
or ODF protein, and Spag4, an axoneme-binding protein, by virtue of their strong interaction with Odf1, the 27 kDa major ODF protein. We proposed a crucial role for leucine zippers in molecular interactions during sperm tail morphogenesis. Here we report the cloning and characterization of a novel gene, Spag5, which encodes a 200 kDa testicular protein that interacts strongly with Odf1. Spag5 is transcribed and translated in pachytene spermatocytes and spermatids. It bears 73% similarity with the mitotic spindle protein Deepest of unknown function. We identified two putative leucine zippers in the C-terminal part of the Spag5 protein, the downstream one of which is involved in interaction with Odf1. Interestingly, these motifs are present in Deepest. These results highlight the importance of the leucine zipper in sperm tail protein interactions. Mol. Reprod. Dev. 59: 410-416, 2001.
