bims-midomi 2025-04-20 papers

BMC Med Genomics. 2025 Apr 18. 18(1): 77

CCT8 drives colorectal cancer progression via the RPL4-MDM2-p53 axis and immune modulation.

Yangyang Teng, Hao Lin, Zijian Lin, Xichen Li, Yejiao Ruan, Binhui Pan, Jinlin Ge, Yuesheng Zhu, Daopo Lin, Qingji Ying, Zhenzhai Cai, Xuanping Xia.

PURPOSE: Colorectal cancer (CRC) ranks high in global mortality, emphasizing the need for effective interventions. The aim of the research is to elucidate the oncogenic role of CCT8 in CRC and its interaction with RPL4 in the RPL4-MDM2-p53 axis.
METHODS: TIMER 2.0, TCGA, and GTEx databases were used to analyze CCT8 expression patterns in CRC. Immunohistochemistry was performed to examine CCT8 distribution in CRC tissues and adjacent non-tumor tissues. Functional assays, including CCK-8, transwell, wound-healing, and flow cytometry, were conducted using DLD-1 and HCT116 cell lines to assess the effects of CCT8 on cell proliferation, migration, invasion, and apoptosis. Gene set enrichment analysis, protein-protein interaction network analysis, and co-immunoprecipitation were performed to explore the interaction between CCT8 and RPL4 and their role in the RPL4-MDM2-p53 pathway. Additionally, gene set variation analysis was applied to investigate the relationship between CCT8/RPL4 expression and immune infiltration patterns in CRC.
RESULTS: CCT8 was significantly upregulated in CRC and associated with tumor progression. Mechanistically, CCT8 potentially synergizes with RPL4 concluded from their positive correlation and similar immune infiltration patterns, influencing the RPL4-MDM2-p53 axis and contributing to p53 ubiquitination and degradation.
CONCLUSION: These findings underscore the oncogenic significance of CCT8 in CRC and shed light on its molecular mechanisms, paving the way for potential therapeutic applications.

Keywords: CCT8; Colorectal cancer; Immune infiltration; RPL4; p53 signaling pathway

DOI: https://doi.org/10.1186/s12920-025-02133-4

Acta Biochim Biophys Sin (Shanghai). 2025 Feb 28. 57(4): 646-655

Iron overload mediates cytarabine resistance in AML by inhibiting the TP53 signaling pathway.

Yan Jia, Ling Li, Ying Li, Xunxun Zhu, Haiyan Wang, Bin Xu, Qiuping Li, Hao Zhang.

Currently, chemotherapy remains the primary treatment for acute myeloid leukemia (AML). Drug resistance in AML cells is a critical factor contributing to the failure of chemotherapy remission and subsequent relapse. Iron overload frequently occurs in AML patients because of hematopoietic suppression or supportive blood transfusion therapy. Previous studies have indicated that iron overload may promote the progression of AML; however, the underlying mechanisms remain unclear. Our results demonstrate that, compared with TP53-wild-type AML cells, TP53-mutant AML cells exhibit increased resistance to cytarabine-induced cytotoxicity. Moreover, reducing TP53 expression in wild-type AML cells diminishes their sensitivity to cytarabine. The TP53 signaling pathway is essential for mediating cytarabine-induced apoptosis in AML cells. In this study, an iron overload model in AML cells via the use of ferric citrate is constructed. Our data indicate that iron overload can suppress the TP53/BCL2/BAX signaling pathway, counteracting cytarabine-induced apoptosis. In TP53 wild-type AML cells, TFR1 participates in iron-mediated resistance to cytarabine by regulating the entry of iron into the cells. These findings provide a foundation for further exploration of the molecular mechanisms involved in AML resistance to cytarabine.

Keywords: TFR1; TP53; acute myeloid leukemia; iron overload

DOI: https://doi.org/10.3724/abbs.2025027

Eur J Med Res. 2025 Apr 18. 30(1): 306

SAP30 promotes clear cell renal cell carcinoma proliferation and inhibits apoptosis through the MT1G axis.

Wei Guo, Shuwen Wang, Zitong Yang, Yu Dong, Zhinan Xia, Wei Xue, Cheng Zhang.

Sin3A-associated protein 30 (SAP30) is a crucial component of the SIN/HDAC histone deacetylase complex and acts as a scaffold that facilitates target gene binding. SAP30 is highly expressed in various tumours; however, its role in renal cell carcinoma (RCC) remains unclear. In our study, we observed the upregulation of SAP30 in clear cell renal cell carcinoma (ccRCC) tissues, and its elevated expression was correlated with a poor prognosis. Previous research has suggested that SAP30 may influence the growth, proliferation, and apoptosis of RCC cells. Gene Ontology (GO) analysis of the downstream regulatory targets of SAP30 revealed that SAP30 suppressed the expression of MT1G, a protein that binds to p53. Mechanistically, SAP30 inhibited MT1G transcription, thereby impairing the function of MT1G in delivering zinc ions to p53, which diminished p53 activity. Moreover, reduced MT1G levels attenuated the inhibitory effect of MT1G on MDM2, further destabilizing p53. Consequently, this cascade promoted RCC progression. In conclusion, our findings indicate that SAP30 inhibits the p53 pathway through MT1G suppression, suggesting that SAP30 and MT1G are potential prognostic markers and therapeutic targets for RCC.

Keywords: MT1G; SAP30; Transcription factor; ccRCC; p53

DOI: https://doi.org/10.1186/s40001-025-02440-7