Aging-related genes related to the prognosis and the immune microenvironment of acute myeloid leukemia

被引:2
作者
Gang, Dongxu [1 ]
Jiang, Yinyan [1 ]
Wang, Xiaofang [1 ]
Zhou, Jifan [1 ]
Zhang, Xiaoyuan [1 ]
He, Xiaoyu [1 ]
Dong, Rujiao [1 ]
Huang, Ziyang [1 ]
Jiang, Songfu [1 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 1, Dept Hematol, Wenzhou 325000, Zhejiang, Peoples R China
关键词
Acute myeloid leukemia; Aging; Biomarker; UCP2; Genipin; Prognosis; OXIDATIVE STRESS; SENESCENCE; CELLS; ROS;
D O I
10.1007/s12094-023-03168-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundAcute myeloid leukemia (AML), one of the common malignancies of the hematologic system, has progressively increased in incidence. Aging is present in both normal tissues and the tumor microenvironment. However, the relationship between senescence and AML prognosis is still not elucidated.MethodsIn this study, RNA sequencing data of AML were obtained from TCGA, and prognostic prediction models were established by LASSO-Cox analysis. Differences in immune infiltration between the different risk groups were calculated using the CIBERSORT and ESTIMATE scoring methods. The KEGG and GO gene enrichment and GSEA enrichment were also used to enrich for differential pathways between the two groups. Subsequently, this study collected bone marrow samples from patients and healthy individuals to verify the differential expression of uncoupling protein 2 (UCP2) in different populations. Genipin, a UCP2 protein inhibitor, was also used to examine its effects on proliferation, cell cycle, and apoptosis in AML cell lines in vitro.ResultsIt showed that aging-related genes (ARGs) expression was correlated with prognosis. And there was a significant difference in the abundance of immune microenvironment cells between the two groups of patients at high risk and low risk. Subsequently, UCP2 expression was found to be elevated in AML patients. Genipin inhibits UCP2 protein and suppresses the proliferation of AML cell lines in vitro.ConclusionARGs can be used as a predictor of prognosis in AML patients. Moreover, suppressing UCP2 can reduce the proliferation of AML cell lines, alter their cell cycle, and promote apoptosis in vitro.
引用
收藏
页码:2991 / 3005
页数:15
相关论文
共 40 条
[1]   Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders [J].
Baker, Darren J. ;
Wijshake, Tobias ;
Tchkonia, Tamar ;
LeBrasseur, Nathan K. ;
Childs, Bennett G. ;
van de Sluis, Bart ;
Kirkland, James L. ;
van Deursen, Jan M. .
NATURE, 2011, 479 (7372) :232-U112
[2]   Similarities and interplay between senescent cells and macrophages [J].
Behmoaras, Jacques ;
Gil, Jesus .
JOURNAL OF CELL BIOLOGY, 2021, 220 (02)
[3]   Aging disrupts circadian gene regulation and function in macrophages [J].
Blacher, Eran ;
Tsai, Connie ;
Litichevskiy, Lev ;
Shipony, Zohar ;
Iweka, Chinyere Agbaegbu ;
Schneider, Kai Markus ;
Chuluun, Bayarsaikhan ;
Heller, H. Craig ;
Menon, Vilas ;
Thaiss, Christoph A. ;
Andreasson, Katrin I. .
NATURE IMMUNOLOGY, 2022, 23 (02) :229-+
[4]   Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies [J].
Chao, Mark P. ;
Takimoto, Chris H. ;
Feng, Dong Dong ;
McKenna, Kelly ;
Gip, Phung ;
Liu, Jie ;
Volkmer, Jens-Peter ;
Weissman, Irving L. ;
Majeti, Ravindra .
FRONTIERS IN ONCOLOGY, 2020, 9
[6]   The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression [J].
Coppe, Jean -Philippe ;
Desprez, Pierre-Yves ;
Krtolica, Ana ;
Campisi, Judith .
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2010, 5 :99-118
[7]   Gal9/Tim-3 expression level is higher in AML patients who fail chemotherapy [J].
Dama, Paola ;
Tang, Marshall ;
Fulton, Noreen ;
Kline, Justin ;
Liu, Hongtao .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2019, 7
[8]   UCP2, a mitochondrial protein regulated at multiple levels [J].
Donadelli, Massimo ;
Dando, Ilaria ;
Fiorini, Claudia ;
Palmieri, Marta .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2014, 71 (07) :1171-1190
[9]   Superoxide activates mitochondrial uncoupling proteins [J].
Echtay, KS ;
Roussel, D ;
St-Pierre, J ;
Jekabsons, MB ;
Cadenas, S ;
Stuart, JA ;
Harper, JA ;
Roebuck, SJ ;
Morrison, A ;
Pickering, S ;
Clapham, JC ;
Brand, MD .
NATURE, 2002, 415 (6867) :96-99
[10]   Prognosis and Characterization of Immune Microenvironment in Acute Myeloid Leukemia Through Identification of an Autophagy-Related Signature [J].
Fu, Denggang ;
Zhang, Biyu ;
Wu, Shiyong ;
Zhang, Yinghua ;
Xie, Jingwu ;
Ning, Wangbin ;
Jiang, Hua .
FRONTIERS IN IMMUNOLOGY, 2021, 12