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

Zeng, Xinyi; Xu, Wenbin; Tong, Jinlu; Liu, Jia; Liu, Mei; Wu, Chao; Yu, Qing; Ye, Chenjing; Wu, Chengyu; Wu, Yingli; Yan, Hua

doi:10.1080/10428194.2022.2086247

Cited by 3 publications

(4 citation statements)

References 32 publications

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“…In addition, we speculate that some mitotic regulatory factors may be involved in this process ( Figure 9 ). During mitosis, PLK1 interacts and phosphorylates the N-terminus of SPAG5 (also known as astrin) [ 38 , 39 , 40 ], which has been reported to upregulate the PI3K/AKT pathway in cancer cells in vitro [ 41 , 42 , 43 , 44 ] through the centrosome protein CEP55 [ 45 ]. In Xenopus , Gwl (MASTL in humans) also interacts with and is phosphorylated by PLK1 during the cell cycle [ 46 ].…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells

Zhao,

Liu,

Tan

et al. 2024

Biology

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E. sinensis is an animal model for studying the reproduction and development of crustaceans. In this study, we knocked down the Es-Kif2a gene by injecting dsRNA into E. sinensis and inhibited Es-Plk1 gene expression by injecting PLK1 inhibitor BI6727 into E. sinensis. Then, the cell proliferation level, apoptosis level, and PI3K/AKT signaling expression level were detected. Our results showed that the proliferation level of spermatogenic cells decreased, while the apoptosis level increased after Es-Kif2a knockdown or Es-Plk1 inhibition. In order to verify whether these changes are caused by regulating the PI3K/AKT pathway, we detected the expression of PI3K and AKT proteins after Es-Kif2a knockdown or Es-Plk1 inhibition. Western Blot showed that in both the Es-Kif2a knockdown group and the Es-Plk1 inhibition group, the expression of PI3K and AKT proteins decreased. In addition, immunofluorescence showed that Es-KIF2A and Es-PLK1 proteins were co-localized during E. sinensis spermatogenesis. To further explore the upstream and downstream relationship between Es-KIF2A and Es-PLK1, we detected the expression level of Es-PLK1 after Es-Kif2a knockdown as well as the expression level of Es-KIF2A after Es-Plk1 inhibition. Western Blot showed that the expression of Es-PLK1 decreased after Es-Kif2a knockdown, while there was no significant change of Es-KIF2A after Es-Plk1 inhibition, indicating that Es-PLK1 may be a downstream factor of Es-KIF2A. Taken together, these results suggest that Es-KIF2A upregulates the PI3K/AKT signaling pathway through Es-PLK1 during the spermatogenesis of E. sinensis, thereby affecting the proliferation and apoptosis levels of spermatogenic cells.

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Section: Discussion and Perspectivesmentioning

confidence: 99%

KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells

Zhao,

Liu,

Tan

et al. 2024

Biology

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“…Based on data from the CoMMpass, we identified 30 candidate genes, the regulation of expression of which may be related to KIAA : AC069499.1 , MYH15 , HNRNPR , KIF11 , CENPI, USP1, CEP78, AMMECR1, RRM1, PLK4, TMPO, SMC4, SGO1, CEP55 , BUB1 , OSBPL11 , KIF4A , CAPG , SPAG5 , INCENP , POLA1 , CDK1 , ZWINT , SMC2 , PCNA , SPATA5, NCAPG2 , GPSM2 , NCAPH and TOP2A. Disturbances in their expression have been the subject of many studies on the pathogenesis of solid tumors, e.g., lung, breast, endometrial, stomach and colon cancer [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, these include genes encoding centromeric proteins ( CENPI ) [ 51 ]; centrosomal proteins ( CEP55 , CEP78 ) [ 52 , 62 ]; motor proteins ( MYH15 , KIF11 ) [ 53 , 54 ] involved in the construction of the karyokinetic spindle or proteins regulating cell division processes ( PLK4, SGO1, BUB1, KIF4A, NCAPG, SPAG5, INCENP, CDK1, ZWINT, NCAPG2, GPSM2, NCAPH and TOP2A ) [ 55 , 60 , 63 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]; and genes encoding proteins involved in DNA repair processes ( USP1, RRM1, KIF4A, POLA1 and PCNA ) [ 58 , 59 , 65 , 74 , 75 ], which are defined as oncogenes ( SPAG5, SMC2 ) [ 67 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

“…SPAG5 gene expression correlates with myeloma cell malignancy, and SPAG5 overexpression is associated with poorer clinical outcomes. In vitro, knockdown of the SPAG5 gene leads to anti-MM effects, cell growth arrest and apoptosis via the PI3K/AKT/mTOR pathway [ 67 ]. The PCNA gene encodes a multifunctional protein which is essential for DNA replication and repair and is overexpressed in myeloma cells.…”

Section: Discussionmentioning

confidence: 99%

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The TT Genotype of the KIAA1524 rs2278911 Polymorphism Is Associated with Poor Prognosis in Multiple Myeloma

Szudy‐Szczyrek

Mlak

Mazurek

et al. 2023

Cells

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Background: The KIAA1524 gene encodes an oncoprotein, CIP2A, which inhibits the phosphorylation of the Akt kinase B, stabilizes the c-Myc protein, and, through that, promotes cancerogenesis. An increase in CIP2A expression has been observed in numerous solid tumors and hematologic malignancies, including multiple myeloma (MM). The aim of our study was to evaluate the clinical impact of the functional single nucleotide polymorphisms (SNP) of the KIAA1524 gene (rs2278911, 686C > T) in MM patients. Methods: The study group consisted of 128 patients with de novo MM. EDTA venous blood samples were collected prior to the treatment. The SNPs were analyzed by Real-Time PCR with the use of specific Taqman probes. Results: Multivariable analysis revealed that variables independently associated with shorter progression-free survival (PFS) included thrombocytopenia, delTP53 and IGH/CCND1 translocation and the TT genotype of the KIAA1524 gene (686C > T) (median PFS: 6 vs. 25 months; HR = 7.18). On the other hand, autologous haematopoietic stem cell transplantation (AHSCT) was related to a lower risk of early disease progression. Moreover, light chain disease, International Staging System (ISS) 3, poor performance status, hypoalbuminemia, IGH/FGFR3 translocation and the TT genotype of the KIAA1524 gene (686C > T) were independent prognostic factors associated with shorter overall survival (OS) (median OS: 8 vs. 45 months; HR = 7.08). Conclusion: The evaluation of the SNP 686C > T of the KIAA1524 gene could be used as a diagnostic tool in MM patients at risk of early disease progression and death.

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SPAG5 Promotes the Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transformation of Colorectal Cancer Cells by Activating the PI3K/AKT Signaling Pathway

Zhang¹,

Zhang²,

Wu³

et al. 2023

Chinese Journal of Physiology

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Colorectal cancer (CRC) is a cancer that occurs in the rectum or colon with a high incidence. Sperm-associated antigen 5 (SPAG5), a gene that regulates cell division, has been observed highly expressed in a variety of cancers, but its role in CRC is unclear. This study aimed to investigate the regulatory role of SPAG5 in CRC. The expression of SPAG5 in multiple cancers and normal tissues was predicted by The Cancer Genome Atlas and Tumor Immune Estimation Resource, and the expression of SPAG5 in human normal intestinal epithelial cells NCM460 and human CRC cell lines Caco2, HT29, SW480, and LOVO was verified by western blotting (WB). The effects of silencing SPAG5 on cell viability, proliferation, and apoptosis were then investigated by cell counting kit-8, WB, and flow cytometry. The effects of silencing SPAG5 on cell migration and invasion were investigated by scratch assay and transwell assay. Finally, the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and AKT in cells were detected by WB. The results showed that SPAG5 was highly expressed in CRC and was verified by WB. Silencing of SPAG5 inhibited cell viability and proliferation and increased the cell apoptosis rate. Furthermore, both cell invasion and migration abilities were suppressed by the low expression of SPAG5. Finally, WB results found that the phosphorylation levels of PI3K and AKT were reduced after SPAG5 silencing. In summary, the results showed that SPAG5 can promote the proliferation and invasion of CRC cells by targeting the PI3K/AKT signaling pathway.

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

Cited by 3 publications

References 32 publications

KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells

KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells

The TT Genotype of the KIAA1524 rs2278911 Polymorphism Is Associated with Poor Prognosis in Multiple Myeloma

SPAG5 Promotes the Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transformation of Colorectal Cancer Cells by Activating the PI3K/AKT Signaling Pathway

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