SLC25A21 Correlates with the Prognosis of Adult Acute Myeloid Leukemia through Inhibiting the Growth of Leukemia Cells Via Downregulating CXCL8

Background

In recent years, targeting mitochondrial apoptosis has emerged as a promising therapeutic strategy for Acute Myeloid Leukemia (AML). The SLC25 family of mitochondrial carriers plays a critical role in maintaining mitochondrial function and regulating apoptosis. However, the role of SLC25A21, an oxodicarboxylate carrier, in AML progression and its potential as a prognostic biomarker remain underexplored. The aim of this study was to further investigate the role, molecular mechanism, and potential clinical value of SLC25A21 in AML progression.

Methods

The transcript levels of SLC25A21 in bone marrow specimens were analyzed using real-time quantitative polymerase chain reaction. The survival analysis was applied to explore the association between SLC25A21 expression and the prognosis of AML.The target genes were detected by RNA sequencing. Functional studies were detected by CCK8, colony formation, cell cycle, apoptosis, reactive oxygen species, and xenograft tumor mouse model.

Results

The results showed that SLC25A21 was downregulated in adult AML, and the low expression of SLC25A21 was correlated with worse prognosis for AML patients. Furthermore, overexpression of SLC25A21 inhibited cell proliferation and cell cycle progression, and was correlated with apoptosis through mitochondrial apoptosis signaling pathway. C-X-C motif chemokine ligand 8 (CXCL8) was identified as a downstream target of SLC25A21. These functions of SLC25A21 could be rescued by the overexpression of CXCL8. Moreover, SLC25A21 overexpression significantly suppressed the growth of xenograft tumors.

Conclusions

SLC25A21 was lowly expressed in adult AML, and the low SLC25A21 expression correlated with poor clinical outcome. The overexpression of SLC25A21 inhibited the AML cell survival and proliferation by dysregulating the expression of CXCL8. SLC25A21 might be a potential prognostic marker and a treatment target for AML.

No relevant conflicts of interest to declare.