Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia

Yang, Wen-Chi; Tsai, Wan–Chi; Lin, Pei; Yang, Mingyu; Liu, Yi-Chang; Chang, Chao-Sung; Yu, Wenhui; Lin, Sheng-Fung

doi:10.1186/1423-0127-20-58

Cited by 29 publications

(37 citation statements)

References 41 publications

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“…Downregulation of BDH2 gene expression in liver cancer causes decreased secretion of acetoacetate, leading to inability to prevent recruitment of tumor-associated macrophage, a step in oncogenic transformation (40). On the other hand, in acute myeloid leukemia (AML) patients BDH2 functions as an anti-apoptotic factor, high expression of which serves as an unfavorable prognostic factor in this disease (41). BDH2 was found to be elevated and positively correlated with TNM stages in patients with esophageal cancers as well (42).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients

et al. 2019

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Kidney is an important organ for ketone body metabolism. However, the role of abnormal ketone metabolism and its possible function in tumorigenesis of clear cell renal cell carcinoma (ccRCC) have not yet been elucidated. Three differentially expressed key enzymes involved in ketone body metabolism, ACAT1, BDH2, and HMGCL, were screened out between ccRCC and normal kidney tissues using the GEO and TCGA databases.We confirmed that the transcription and protein expression of ACAT1, BDH2, and HMGCL were significantly lower in ccRCC by real-time RT-PCR and IHC assays. Those patients with lower expression of these three genes have a worse outcome. In addition, we demonstrated that ectopic expression of each of these genes inhibited the proliferation of ccRCC cells. The overexpressed ACAT1 and BDH2 genes remarkably impeded the migratory and invasive capacity of ccRCC cells. Furthermore, exogenous β-hydroxybutyrate suppressed the growth of ccRCC cells in vitro in a dose-dependent manner. Our findings suggest that ACAT1, BDH2, and HMGCL are potential tumor suppressor genes, and constitute effective prognostic biomarkers for ccRCC. Ketone body metabolism might thus be a promising target in a process for developing novel therapeutic approaches to treat ccRCC.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients

et al. 2019

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“…Currently, few lncRNAs are known to be associated with the latter two pathways of cell death in EC, but several lncRNAs are involved in apoptosis via regulating the transcription of key apoptotic factors. For instance, BDH2, which functions as an anti-apoptotic factor, is regulated by survivin via the caspase-3-independent pathway [ 125 ]. P73 antisense RNA 1T (TP73-AS1), a lncRNA mapped to chromosome 1p36.32, was shown to mediate apoptosis via BDH2 [ 126 ].…”

Section: Involvement Of Lncrnas In the Hallmarks Of Cancermentioning

confidence: 99%

Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and potential applications

Xiao

et al. 2018

J Hematol Oncol

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Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. The lack of early diagnostic biomarkers and effective prognostic indicators for metastasis and recurrence has resulted in the poor prognosis of EC. In addition, the underlying molecular mechanisms of EC development have yet to be elucidated. Accumulating evidence has demonstrated that lncRNAs play a vital role in the pathological progression of EC. LncRNAs may regulate gene expression through the recruitment of histone-modifying complexes to the chromatin and through interactions with RNAs or proteins. Recent evidence has demonstrated that the dysregulation of lncRNAs plays important roles in the proliferation, metastasis, invasion, angiogenesis, apoptosis, chemoradiotherapy resistance, and stemness of EC, which suggests potential clinical implications. In this review, we highlight the emerging roles and regulatory mechanisms of lncRNAs in the context of EC and discuss their potential clinical applications as diagnostic and prognostic biomarkers.

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“…This increases an oxidative stress signature ( 143 ). Intriguingly, the expression of BDH2 negatively correlated with patient survival suffering from normal acute myeloid leukemia ( 144 ). However, regarding the clinical importance of siderophores, especially in tumors, more investigations are needed.…”

Section: Lcn-2 May Function As An Iron Transporter In the Tumor Micromentioning

confidence: 99%

Iron Handling in Tumor-Associated Macrophages—Is There a New Role for Lipocalin-2?

et al. 2017

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Carcinogenesis is a multistep process. Besides somatic mutations in tumor cells, stroma-associated immunity is a major regulator of tumor growth. Tumor cells produce and secrete diverse mediators to create a local microenvironment that supports their own survival and growth. It is becoming apparent that iron acquisition, storage, and release in tumor cells is different from healthy counterparts. It is also appreciated that macrophages in the tumor microenvironment acquire a tumor-supportive, anti-inflammatory phenotype that promotes tumor cell proliferation, angiogenesis, and metastasis. Apparently, this behavior is attributed, at least in part, to the ability of macrophages to support tumor cells with iron. Polarization of macrophages by apoptotic tumor cells shifts the profile of genes involved in iron metabolism from an iron sequestering to an iron-release phenotype. Iron release from macrophages is supposed to be facilitated by ferroportin. However, lipid mediators such as sphingosine-1-phosphate, released form apoptotic tumor cells, upregulate lipocalin-2 (Lcn-2) in macrophages. This protein is known to bind siderophore-complexed iron and thus, may participate in iron transport in the tumor microenvironment. We describe how macrophages handle iron in the tumor microenvironment, discuss the relevance of an iron-release macrophage phenotype for tumor progression, and propose a new role for Lcn-2 in tumor-associated macrophages.

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Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia

Cited by 29 publications

References 41 publications

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients

Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and potential applications

Iron Handling in Tumor-Associated Macrophages—Is There a New Role for Lipocalin-2?

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