Li Junnan, Yan Xinyu, Ding Li, Yin Jiaxiu, Li Ping, Liu Lin
Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Orthopaedics, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
Front Pharmacol. 2025 Jun 4;16:1572621. doi: 10.3389/fphar.2025.1572621. eCollection 2025.
Sperm - associated antigen 6 (SPAG6), a member of the cancer/testis antigen (CTA) family, has been linked to multiple hematologic malignancies. Nevertheless, its role in multiple myeloma (MM) remains unclear.
Bioinformatics, tissue specimens from plasma cell tumors, and bone marrow samples of MM patients were utilized to evaluate SPAG6 expression and to analyze its correlations with clinical features and prognosis. , RNA interference was applied to downregulate SPAG6 in U266 cells and upregulate it in RPMI - 8226 cells, and then its impacts on cell proliferation, apoptosis, and migration were investigated. Transcriptome sequencing data were comprehensively analyzed to elucidate the mechanism of SPAG6 in MM cells.
SPAG6 was positively expressed in MM cell lines, plasma cell tumor tissue specimens, and MM patient bone marrow samples. The mRNA expression of SPAG6 in MM patients was upregulated relative to the control group and was correlated with blood calcium levels, plasma cell ratio, and skeletal infiltration. , SPAG6 overexpression promoted cell proliferation, migration, and the resistance to apoptosis in MM cells, while down - expression had contrary effects. Mechanistic studies revealed that SPAG6 directly interacts with dual-specificity phosphatase 1 (DUSP1). Furthermore, SPAG6 was found to modulate the expression of downstream proteins in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway by regulating DUSP1 activity.
Overall, this study highlights that SPAG6 may serve as a potential therapeutic target for MM by regulating DUSP1 expression to activate the MAPK/ERK signaling pathway.
精子相关抗原6（SPAG6）是癌胚抗原（CTA）家族的成员，与多种血液系统恶性肿瘤有关。然而，其在多发性骨髓瘤（MM）中的作用仍不清楚。
利用生物信息学、浆细胞瘤组织标本和MM患者的骨髓样本评估SPAG6的表达，并分析其与临床特征和预后的相关性。应用RNA干扰下调U266细胞中的SPAG6并上调RPMI - 8226细胞中的SPAG6，然后研究其对细胞增殖、凋亡和迁移的影响。对转录组测序数据进行综合分析，以阐明SPAG6在MM细胞中的作用机制。
SPAG6在MM细胞系、浆细胞瘤组织标本和MM患者骨髓样本中呈阳性表达。MM患者中SPAG6的mRNA表达相对于对照组上调，且与血钙水平、浆细胞比例和骨骼浸润相关。SPAG6过表达促进MM细胞的增殖、迁移和抗凋亡能力，而低表达则产生相反的效果。机制研究表明，SPAG6直接与双特异性磷酸酶1（DUSP1）相互作用。此外，发现SPAG6通过调节DUSP1活性来调节丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）信号通路中下游蛋白的表达。
总体而言，本研究强调SPAG6可能通过调节DUSP1表达以激活MAPK/ERK信号通路而成为MM的潜在治疗靶点。
