Metallothionein protein and minichromosome maintenance protein-2 expression in adrenocortical tumors

Saiegh, Leonard; Sheikh‐Ahmad, Mohammad; Shechner, Carmela; Reut, Maria; Darawsha, Yusef; Zolotov, Sagit; Shefer, Hila Kreizman; Bejar, Ilan; Bejar, Jacob

doi:10.1016/j.ando.2019.09.003

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…Certain previous studies have revealed that Ki-67 and minichromosome maintenance protein are reliable indicators of benign and malignant adrenal tumors (51,52). Additionally, various studies have used pituitary-tumor transforming gene 1 (53), telomerase activity (54) and vascular endothelial growth factor (55) as diagnostic markers of ACC.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma

Zhang

Miao

et al. 2020

Exp Ther Med

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The molecular mechanisms of adrenocortical carcinoma (ACC) carcinogenesis and progression remain unclear. In the present study, three microarray datasets from the Gene Expression Omnibus database were screened, which identified a total of 96 differentially expressed genes (DEGs). A protein-protein interaction network (PPI) was established for these DEGs and module analysis was performed using STRING and Cytoscape. A total of eight hub genes were identified from the most significant module; namely, calponin 1 (CNN1), myosin light chain kinase (MYLK), cysteine and glycine rich protein 1 (CSRP1), myosin heavy chain 11 (MYH11), fibulin extracellular matrix protein 2 (EFEMP2), fibulin 1 (FBLN1), microfibril associated protein 4 (MFAP4) and fibulin 5 (FBLN5). The biological functions of these hub genes were analyzed using the DAVID online tool. Changes in the expression of hub genes did not affect overall survival; however, downregulated EFEMP2 decreased disease-free survival. CSRP1 and MFAP4 expression levels were associated with adverse clinicopathological features. In conclusion, although all eight hub genes were downregulated in ACC, they appeared to have important functions in ACC carcinogenesis and progression. Identification of these genes complements the genetic expression profile of ACC and provides insight for the diagnosis, treatment and prognosis of ACC.

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Section: Discussionmentioning

confidence: 99%

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma

Zhang

Miao

et al. 2020

Exp Ther Med

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“…This evidence reveals not only the single-locus effect but a joint effect of SNPs in different MT genes on HDP susceptibility, yet the mechanisms remain to be further elucidated. It has been shown that the differential expression levels of MT isoforms present in different diseases and tumor types ( Aquime et al, 2020 ; Hung et al, 2019 ; Saiegh et al, 2019 ; Sampaio et al, 2019 ), suggesting that MT isoforms may play distinct roles in pathophysiological processes under extreme conditions. MTs are highly evolutionarily conserved but non-essential; the antioxidative action of MTs is far stronger than that of superoxide dismutase (SOD) and GSH ( Ma'Rifah et al, 2019 ; Thornalley and Vasak, 1985 ), and the latter is required for the recycling of oxidative and reduced forms of MTs ( Kang, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study

Wei

Wen

et al. 2022

Front. Genet.

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Background: The involvement of oxidative stress in the pathological process of hypertensive disorders of pregnancy (HDP) gives rise to the interest in exploring the association of genetic variations in antioxidant metallothionein (MT) genes with HDP susceptibility.Methods: Seventeen single-nucleotide polymorphisms(SNPs) in MT genes were selected to conduct genotyping based on a case-control study consisting of 371 HDP cases (pregnancy with chronic hypertension (66), gestational hypertension (172), and preeclampsia or preeclampsia superimposed on chronic hypertension (133)) and 479 controls. The association between SNPs in MTs and the risk of HDP was estimated with unconditional logistic regression analysis and further tested with the false-positive report probability (FPRP) procedure. The joint effects of SNPs on the HDP risk were assessed by haplotype analysis.Results: After the adjustment for age and pre-pregnancy body mass index (pre-BMI) in the logistic regress analysis and followed by the FPRP test, the genetic variation rs10636 (OR = 0.46, 95% CI: 0.30–0.71 for GG vs. CC, p = 0.000 and OR = 0.48, 95% CI: 0.32–0.73 for GG vs. CG/CC, p = 0.001) in MT2A was associated with gestational hypertension. Other four SNPs, that is, rs11076161 (OR = 1.89, 95% CI: 1.35–2.63 for GG vs. GA/AA, p = 0.000) in MT1A; rs7191779 (OR = 1.54, 95% CI: 1.11–2.13 for CC vs. CG/GG, p = 0.010) in MT1B; rs8044719 (OR = 0.57, 95% CI: 0.40–0.80 for GT vs. GG, p = 0.001) in MT1DP; and rs8052334 (OR = 1.52, 95% CI: 1.10–2.11 for TT vs. TC/CC, p = 0.012) in MT1B were significantly associated with the susceptibility of HDP. The haplotype analysis among 11, 10, 10, and seven SNPs in MT (MT1A, MT2A, MT1M, MT1B, and MT1DP) genes showed that eight (A-C-G-T-C-G-A-G-C-G-C, OR = 4.559; A-C-T-C-C-C-A-G-C-G-C, OR = 5.777; A-C-T-T-C-G-A-G-C-G-C, OR = 4.590; G-A-T-C-C-G-C-G-G-C-C, OR = 4.065; G-A-T-C-G-C-C-G-G-C-C, OR = 4.652; G-A-T-T-C-C-C-G-G-C-C, OR = 0.404; G-C-T-C-C-C-A-G-G-C-C, OR = 1.901; G-C-T-T-C-C-A-G-G-C-C, and OR = 3.810), five (C-G-A-T-C-A-C-C-G-G, OR = 2.032; C-G-A-T-C-G-C-C-G-G, OR = 2.077; G-A-C-T-C-A-C-C-T-G, OR = 0.564; G-G-A-G-C-A-C-C-G-G, OR = 5.466; G-G-A-T-T-A-G-C-G-G, and OR = 0.284), five (A-C-G-T-C-G-A-G-C-C, OR = 2.399; A-C-T-C-C-C-C-T-G-G, OR = 0.259; G-A-T-C-C-C-C-G-G-C, OR = 1.572; G-A-T-C-G-C-C-G-G-C, OR = 0.001; G-C-T-C-G-C-A-G-G-C, and OR = 2.512), and five (A-C-T-C-C-C-G, OR = 0.634; G-A-G-C-C-C-G, OR = 4.047; G-A-T-T-G-C-G, OR = 0.499; G-C-G-T-C-A-G, and OR = 7.299; G-C-T-C-C-A-G, OR = 1.434) haplotypes were significantly associated with pregnancy with chronic hypertension, gestational hypertension, preeclampsia, or preeclampsia superimposed on chronic hypertension and HDP.Conclusion: These variant MT alleles and their combination patterns may be used as genetic markers for predicting HDP susceptibility.

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“…Multiple studies have shown that MT2A expression is vital for the development of cancer. On the one hand, MT2A is a pro-oncogene in breast cancer [27], prostate cancer [28], large B cell lymphoma [29], and adrenocortical cancer [30], and closely related with unfavorable prognosis of numerous malignant tumors. On the other hand, the decreased expression level of MT2A in gastric cancer [31], liver cancer [32], and thyroid cancer [33] are negatively correlated with cancer mortality.…”

Section: Discussionmentioning

confidence: 99%

Effect of MT2A on apoptosis and proliferation in HL60 cells

et al. 2021

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Although accumulating evidence has revealed that metallothioneins (MTs) and its family member MT2A are strongly linked to the risk of various solid tumors, researches on the occurrence and development of acute myeloid leukemia (AML) have rarely been investigated. Here, we constructed a lentiviral vector with MT2A over-expression and the interfering plasmids with MT2A expression inhibition to study the influence of MT2A on the bioactivities of HL60 cells. After cells were infected with a lentiviral vector containing the MT2A gene, both transcription and translation levels of MT2A were significantly increased in the over-expressed group in comparison with control groups. In vitro experiments, all results demonstrated that cell reproductive capacity was inhibited, but cell apoptosis rate was significantly increased. Together, the expression of apoptosis-related protein Bcl2 was remarkably reduced, while a high expression level of Bax protein was detected. Further experiments revealed that up-regulation of MT2A induced cell apoptosis and promoted G2/M phase arrest. The mechanism may be associated with down-regulated p-IκB-α and cyclinD1 expression and up-regulated IκB-α expression in the nuclear factor-kappaB (NF-κB) pathway. On the contrary, MT2A expression was down-regulated by interfering plasmids. We found that cell proliferative potential was notably increased in the interfering group compared with the negative and untreated group. What's more, MT2A may be closely related to AML cell proliferation and function via the NF-κB signal pathway.

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Metallothionein protein and minichromosome maintenance protein-2 expression in adrenocortical tumors

Cited by 6 publications

References 35 publications

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma

Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study

Effect of MT2A on apoptosis and proliferation in HL60 cells

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