MT1G serves as a tumor suppressor in hepatocellular carcinoma by interacting with p53

Wang, Yingchao; Wang, Gaoxiong; Tan, Xionghong; Ke, Kun; Zhao, Bixing; Cheng, Niangmei; Dang, Yuan; Liao, Naishun; Wang, Fei; Zheng, Xiaoyuan; Li, Qin; Liu, Xiaolong; Liu, Jingfeng

doi:10.1038/s41389-019-0176-5

Cited by 37 publications

(24 citation statements)

References 46 publications

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“…Interestingly, decreased expression of MT1 genes was reported in a wide range of neoplasms of different organs including breast, colon, stomach, lung and prostate. 32 Importantly, MT1 genes exert tumor suppressor activity in a number of malignancies, such as hepatocellular carcinoma (MT1X, MT1M, MT1H and MT1G), [35][36][37][38] prostate cancer (MT1H and MT1E) 39,40 and thyroid cancer (MT1G, MT1M). 41,42 Given the onco-suppression feature of MT1 genes, it is possible that their over-expression promoted apoptosis in the ZnO NPs-treated K562 cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Transcriptomics-Based Characterization of the Toxicity of ZnO Nanoparticles Against Chronic Myeloid Leukemia Cells</p>

Alsagaby¹,

Vijayakumar²,

Premanathan³

et al. 2020

IJN

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Introduction: Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach. Objective: The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action. Methods: We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells. Results: ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells (p≤0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥4 and p≤0.008 with corrected p≤0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in "response to zinc", "response to toxic substance" and "negative regulation of growth" (corrected p≤0.05). In contrast, the repressed genes positively regulated "cell proliferation", "cell migration", "cell adhesion", "receptor signaling pathway via JAK-STAT" and "phosphatidylinositol 3-kinase signaling" (corrected p≤0.05). Lowering the FC to ≥1.5 with p≤0.05 and corrected p≤0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway. Conclusion: Taken together, our findings support the earlier studies that reported anticancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells.

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Section: Discussionmentioning

confidence: 99%

<p>Transcriptomics-Based Characterization of the Toxicity of ZnO Nanoparticles Against Chronic Myeloid Leukemia Cells</p>

Alsagaby¹,

Vijayakumar²,

Premanathan³

et al. 2020

IJN

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“…CARS1 knockdown has been proven to suppress ferroptosis induced by cysteine deprivation and promote the transsulfuration pathway (45). MT1G, a small-molecular weight protein that has high affinity for zinc ions, can inhibit proliferation by increasing the stability and transcriptional activity of p53 (46). PTGS2, also known as cyclooxygenase 2, is associated with prostanoid biosynthesis (47).…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Prognostic Signature for Prostate Cancer Based on Ferroptosis-Related Genes

et al. 2021

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Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, ferroptosis related genes (FRGs) in prostate cancer (PCa) are not been well studied. In this study, we collected the mRNA expression profiles and clinical information of PCa patients from TCGA and MSKCC databases. The univariate, LASSO, and multivariate Cox regression analyses were performed to construct a prognostic signature. Seven FRGs, AKR1C3, ALOXE3, ATP5MC3, CARS1, MT1G, PTGS2, and TFRC, were included to establish a risk model, which was validated in the MSKCC dataset. The results showed that the high-risk group was apparently correlated with copy number alteration load, tumor burden mutation, immune cell infiltration, mRNAsi, immunotherapy, and bicalutamide response. Moreover, we found that TFRC overexpression induced the proliferation and invasion of PCa cell lines in vitro. These results demonstrate that this risk model can accurately predict prognosis, suggesting that FRGs are promising prognostic biomarkers and potential drug targets in PCa patients.

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“…In HCC, the expression of most MT1 family are significantly down-regulated, and will affect the occurrence and development of HCC [ 8 ]. With regard to the four MT1s we identified, studies have confirmed that the expression of MT1G could serve as tumor suppressor by inhibiting cell proliferation and enhancing apoptosis in HCC [ 25 ]; MT1F was proven to inhibit the HCC cell growth [ 26 ]; Liu et al demonstrated that MT1X is probably a prognostic biomarker and reduces the progression and metastasis of HCC [ 27 ]. Likewise, we validated that four MT1s were all downregulated in HCC with MT1 deletion.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion

Zhang¹,

Hao²,

Wang³

et al. 2021

Pathol. Oncol. Res.

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Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Metallothioneins (MTs) are metal-binding proteins involved in multiple biological processes such as metal homeostasis and detoxification, as well as in oncogenesis. Copy number variation (CNV) plays a vital role in pathogenesis and carcinogenesis. Nevertheless, there is no study on the role of MT1 CNV in HCC.Methods: Array-based Comparative Genomic Hybridization (aCGH) analysis was performed to obtain the CNV data of 79 Guangxi HCC patients. The prognostic effect of MT1-deletion was analyzed by univariate and multivariate Cox regression analysis. The differentially expressed genes (DEGs) were screened based on The Gene Expression Omnibus database (GEO) and the Liver Hepatocellular Carcinoma of The Cancer Genome Atlas (TCGA-LIHC). Then function and pathway enrichment analysis, protein-protein interaction (PPI) and hub gene selection were applied on the DEGs. Lastly, the hub genes were validated by immunohistochemistry, tissue expression and prognostic analysis.Results: The MT1-deletion was demonstrated to affect the prognosis of HCC and can act as an independent prognostic factor. 147 common DEGs were screened. The most significant cluster of DEGs identified by Molecular Complex Detection (MCODE) indicated that the expression of four MT1s were down-regulated. MT1X and other five hub genes (TTK, BUB1, CYP3A4, NR1I2, CYP8B1) were associated with the prognosis of HCC. TTK, could affect the prognosis of HCC with MT1-deletion and non-deletion. NR1I2, CYP8B1, and BUB1 were associated with the prognosis of HCC with MT1-deletion.Conclusions: In the current study, we demonstrated that MT1-deletion can be an independent prognostic factor in HCC. We identified TTK, BUB1, NR1I2, CYP8B1 by processing microarray data, for the first time revealed the underlying function of MT1 deletion in HCC, MT1-deletion may influence the gene expression in HCC, which may be the potential biomarkers for HCC with MT1 deletion.

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MT1G serves as a tumor suppressor in hepatocellular carcinoma by interacting with p53

Cited by 37 publications

References 46 publications

<p>Transcriptomics-Based Characterization of the Toxicity of ZnO Nanoparticles Against Chronic Myeloid Leukemia Cells</p>

<p>Transcriptomics-Based Characterization of the Toxicity of ZnO Nanoparticles Against Chronic Myeloid Leukemia Cells</p>

Identification and Validation of a Prognostic Signature for Prostate Cancer Based on Ferroptosis-Related Genes

Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion

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