Nrf2 signaling pathway in trace metal carcinogenesis: A cross-talk between oxidative stress and angiogenesis

Sereshki, Nasrin; Malakoutikhah, Zahra; Dehkordi, Sayed Ali Ehsan; Fahim, Alireza; Mohammadzadeh, Samane; Maghool, Fatemeh

doi:10.1016/j.cbpc.2022.109266

Cited by 14 publications

(6 citation statements)

References 152 publications

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“…Although Nrf2 may play a dual role in cancer, acting as an oncogene or tumor suppressor [ 37 , 38 ], studies have indicated that constitutive activation of Nrf2 may deliver selective advantages to cells that promote their adaptation to adverse growth conditions for cancer formation [ 39 , 40 , 41 ]. Nrf2 is associated with cancer invasion, chemoresistance, radioresistance, and poor clinical prognosis in many cancers [ 41 , 42 , 43 , 44 ]. Furthermore, Nrf2 is activated by various oncogenic kinases, such as GSK3β, PI3-AKT, and MAPK [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway

You

Chang

et al. 2022

Cells

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The MYH9 (Myosin heavy chain 9), an architecture component of the actomyosin cytoskeleton, has been reported to be dysregulated in several types of cancers. However, how this molecule contributes to cancer development is still obscure. This study deciphered the molecular function of MYH9 in head and neck cancer (HNC). Cellular methods included clonogenic survival, wound-healing migration, and Matrigel invasion assays. Molecular techniques included RT-qPCR, western blot, luciferase reporter assays, and flow cytometry. Clinical association studies were undertaken by TCGA data mining, Spearman correlation, and Kaplan-Meier survival analysis. We found that MYH9 was overexpressed in tumors and associated with poor prognosis in HNC patients. MYH9 promoted cell motility along with the modulation of the extracellular matrix (fibronectin, ITGA6, fascin, vimentin, MMPs). Also, MYH9 contributed to radioresistance and was related to the expression of anti-apoptotic and DNA repairing molecules (XIAP, MCL1, BCL2L1, ATM, RAD50, and NBN). Mechanically, MYH9 suppressed cellular ROS levels, which were achieved by activating the pan-MAPK signaling molecules (Erk, p38, and JNK), the induction of Nrf2 transcriptional activity, and the up-regulation of antioxidant enzymes (GCLC, GCLM, GPX2). The antioxidant enzyme GCLC was further demonstrated to facilitate cell invasion and radioresistance in HNC cells. Thus, MYH9 exerts malignant functions in HNC by regulating cellular ROS levels via activating the MAPK-Nrf2-GCLC signaling pathway. As MYH9 contributes to radioresistance and metastasis, this molecule may serve as a prognostic biomarker for clinical application. Furthermore, an in vivo study is emergent to support the therapeutic potential of targeting MYH9 to better manage refractory cancers.

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Section: Discussionmentioning

confidence: 99%

MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway

You

Chang

et al. 2022

Cells

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“…The Perl language was used to convert the form of data expression (Ensembl ID transformation to Gene Symbol) of the samples and distinguish between mRNA and lncRNA in every sample. The cuproptosis-related genes were identified from three studies [ 6 , 14 , 15 ]. All the revisions have been appropriately made.…”

Section: Methodsmentioning

confidence: 99%

A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma

Wu,

Yao,

Jia

et al. 2023

Heliyon

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“…Cuproptosis-Related Genes. Tsvetkov et al, Deng et al, and Emami et al proposed key genes involved in the tumor copper death mechanism, including ATP7A, ATP7B, CDKN2A, DBT, DLAT, DLD, DLST, FDX1, GCSH, GLS, LIAS, LIPT1, LIPT2, MTF1, NFE2L2, NLRP3, PDHA1, PDHB, and SLC31A1 [7,11,12]. The cuproptosis-related genes coexpressed with cuproptosis genes were obtained based on TCGA-PAAD samples.…”

Section: Identification Ofmentioning

confidence: 99%

A Novel Cuproptosis‐Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

Jiang

Hou

et al. 2023

BioMed Research International

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Background. Pancreatic cancer (PAAD) is a malignant tumor with a poor prognosis and lacks sensitive biomarkers for diagnosis and targeted therapy. Cuproptosis, a recently proposed form of cell death based on cellular copper ion concentration, plays a key role in cancer biology. This study is aimed at constructing a risk model for predicting the prognosis of PAAD patients based on cuproptosis-related genes. Methods. Pancreatic-related data from UCSC-TCGA and UCSC-GTEx databases were extracted for analysis, and TCGA-PAAD samples were randomly divided into the training and validation groups. Pearson correlation analysis was used to obtain cuproptosis-related genes coexpressed with 19 copper death genes. Univariate Cox and Lasso regression analyses were used to obtain cuproptosis-related prognostic genes. Multivariate Cox regression analysis was used to construct the final prognostic risk model. The risk score curve, Kaplan-Meier survival curves, and ROC curve were used to evaluate the predictive ability of the Cox risk model. Finally, the functional annotation of the risk model was obtained through enrichment analysis. Results. The Cox risk model has an eight prognostic cuproptosis-related gene signature. Kaplan-Meier survival curves demonstrated that the high-risk group had a shorter survival time. The ROC curve of the risk score was well created to predict one-, three-, and five-year survival rates, and AUC of the risk score was higher than other clinical characteristics. Cox regression analysis revealed that the risk score has an independent prognostic value for PAAD. GSEA reveals specific tumor pathways associated with the risk model (Myc targets v1, mTORC1 signaling, and E2F targets). Conclusions. We constructed a prognostic model containing eight cuproptosis-related genes (AKR1B10, KLHL29, PROM2, PIP5K1C, KIF18B, AMIGO2, MRPL3, and PI4KB) that can accurately predict the prognosis of PAAD patients. The results will provide new perspectives for individualized outcome prediction and new therapy development for PAAD patients.

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Nrf2 signaling pathway in trace metal carcinogenesis: A cross-talk between oxidative stress and angiogenesis

Cited by 14 publications

References 152 publications

MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway

MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway

A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma

A Novel Cuproptosis‐Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

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