SPAG5 as a novel biomarker and potential therapeutic target via regulating AKT pathway in multiple myeloma
SPAG5 as a novel biomarker and potential therapeutic target via regulating AKT pathway in multiple myeloma
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DOI：
10.1080/10428194.2022.2086247
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发表时间：
2022-06
影响因子：
2.6
通讯作者：
Xinyi Zeng;Wenbin Xu;Jianjing Tong;Jia Liu;Zilu Zhang;Mei Liu;Chao Wu;Qing Yu;C. Ye
中科院分区：
文献类型：
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作者：
Xinyi Zeng;Wenbin Xu;Jianjing Tong;Jia Liu;Zilu Zhang;Mei Liu;Chao Wu;Qing Yu;C. Ye
摘要 SPAG5作为有丝分裂中的纺锤体相关蛋白，已被观察到在实体瘤中具有致癌活性。在这里，我们发现SPAG5表达与浆细胞恶性肿瘤的恶化相关，并且SPAG5过度表达（OE）预测多发性骨髓瘤（MM）的不利结果。 SPAG5 敲除通过调节细胞生长和凋亡在 MM 细胞系和动物异种移植模型中产生抗 MM 作用。此外，基因集富集分析（GSEA）显示，PI3K/AKT/mTOR 通路在 GSE 数据集中高表达 SPAG5 的 MM 样本中富集。 AKT/mTOR 通路中的磷酸化水平同时下调。然而，在用 AKT 抑制剂 MK2206 处理后，SPAG5 的 OE 可以恢复 MM 细胞的细胞生长和 p-AKT 水平。总而言之，SPAG5 可以作为一种新型生物标志物，并且靶向 SPAG5 可能具有治疗 MM 的潜力。
Abstract SPAG5, as a spindle-associated protein in mitosis, has been observed to have oncogenic activities in solid tumors. Here, we identified that SPAG5 expression was correlated with the deterioration of plasma cell malignancy and SPAG5 overexpression (OE) predicted unfavorable outcomes in multiple myeloma (MM). SPAG5 knockdown led to anti-MM effects in MM cell lines and animal xenograft models by regulating cell growth and apoptosis. Furthermore, gene set enrichment analysis (GSEA) revealed that PI3K/AKT/mTOR pathway was enriched in MM samples with highly expressed SPAG5 from GSE datasets. There was a concurrent downregulation of phosphorylation levels in the AKT/mTOR pathway. Yet OE of SPAG5 could restore the cell growth and p-AKT levels in MM cells after treatment with the AKT inhibitor MK2206. Taken together, SPAG5 could serve as a novel biomarker, and targeting the SPAG5 might have therapeutic potential in MM.