Department of Basic Medical Sciences, Qinghai University, Xi'ning, China.
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xi'ning, China.
DNA Cell Biol. 2022 Oct;41(10):893-902. doi: 10.1089/dna.2021.0531.
The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy.
精子相关抗原 5（SPAG5）是有丝分裂和细胞周期检查点调节中的一种重要蛋白，作为各种癌症中的新型癌基因受到越来越多的关注。我们在临床胃癌（GC）样本和癌症基因组图谱 GC 数据中检测到 SPAG5 表达水平升高。然而，SPAG5 在 GC 中的生物功能和潜在机制仍不清楚。在本研究中，我们研究了 SPAG5 在 GC 发展中的作用以及 SPAG5 与 5-氟尿嘧啶（5-FU）治疗的相关性。与正常组织相比，GC 样本中 SPAG5 的表达增加（80.8%比 22.0%），这与预后不良明显相关。生物学实验表明，SPAG5 敲低诱导细胞和动物模型中的细胞凋亡并抑制增殖。下调 SPAG5 增强了 GC 细胞对 5-FU 的敏感性。基因微阵列芯片鉴定出 SPAG5 沉默细胞中 856 个上调和 787 个下调基因。此外，使用 ingenuity 通路分析，12 个显著基因，包括 CDKN1A、CDKN1B、EIF4E、MAPK1 和 HSP90B1，属于 PI3K/AKT 信号通路。同时，实时 PCR 和 Western blot 结果表明，SPAG5 敲低抑制了 PI3K/AKT 信号通路。综上所述，SPAG5 通过调节 PI3K/AKT 信号通路促进 GC 细胞的生长，它可能是 GC 治疗中有前途的靶基因。
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