SPAG5 as a novel biomarker and potential therapeutic target via regulating AKT pathway in multiple myeloma.

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.

• Authors: Xinyi Zeng, Wenbin Xu, Jianjing Tong, Jia Liu, Zilu Zhang, Mei Liu, Chao Wu, Qing Yu, Chenjing Ye, Chengyu Wu, Yingli Wu, Hua Yan
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 63 Issue 11 Pg. 2565-2572 (11 2022) ISSN: 1029-2403 [Electronic] United States
• PMID: 35730922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• Cell Cycle Proteins
• TOR Serine-Threonine Kinases
• Biomarkers
• SPAG5 protein, human

Topics

• Animals
• Humans
• Proto-Oncogene Proteins c-akt (metabolism)
• Multiple Myeloma (drug therapy, genetics)
• Phosphatidylinositol 3-Kinases (metabolism)
• Signal Transduction
• Cell Cycle Proteins (metabolism)
• Cell Line, Tumor
• TOR Serine-Threonine Kinases (metabolism)
• Cell Proliferation (genetics)
• Apoptosis
• Biomarkers