The inhibition of chloride intracellular channel 1 enhances Ca2+ and reactive oxygen species signaling in A549 human lung cancer cells

Lee, Jae-Rin; Lee, Jong-Yoon; Kim, Hyunji; Hahn, Myong‐Joon; Kang, Jong‐Sun; Cho, Hana

doi:10.1038/s12276-019-0279-2

Cited by 16 publications

(12 citation statements)

References 60 publications

(57 reference statements)

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“…This is likely because, in contrast to solid malignancies, aggressive leukemias like AML depend on cellular oxidative phosphorylation for proliferation which is supported by upregulation of respiratory complex genes(47). Various studies also suggest dysregulation of chloride ion channels such as the CLIC1 gene which plays a role in drug resistance and progression of various malignancies(22, 48). Although, the role of CLIC1 in AML is still unexplored, we observed significant upregulation of CLIC1 in paediatric AML with adverse prognostic impact.…”

Section: Discussionmentioning

confidence: 99%

Decoding mitochondrial genes in pediatric AML and development of a novel prognostic mitochondrial gene signature

Chaudhary

Ganguly

Palanichamy

et al. 2022

Preprint

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Background: Gene expression profile of mitochondrial-related genes is not well deciphered in pediatric acute myeloid leukaemia (AML). We aimed to identify mitochondria-related differentially expressed genes (DEGs) in pediatric AML with their prognostic significance. Methods: Children with de novo AML were included prospectively between July 2016-December 2019. Transcriptomic profiling was done for a subset of samples, stratified by mtDNA copy number. Top mitochondria-related DEGs were identified and validated by real-time PCR. A prognostic gene signature risk score was formulated using DEGs independently predictive of overall survival (OS) in multivariable analysis. Predictive ability of the risk score was estimated along with external validation in The Tumor Genome Atlas (TCGA) AML dataset. Results: In 143 children with AML, twenty mitochondria-related DEGs were selected for validation, of which 16 were found to be significantly dysregulated. Upregulation of SDHC (p<0.001), CLIC1 (p=0.013) and downregulation of SLC25A29 (p<0.001) were independently predictive of inferior OS, and included for developing prognostic risk score. The risk score model was independently predictive of survival over and above ELN risk categorization (Harrell's c-index: 0.675). High-risk patients (risk score above median) had significantly inferior OS (p<0.001) and event free survival (p<0.001); they were associated with poor-risk cytogenetics (p=0.021), ELN intermediate/poor risk group (p=0.016), absence of RUNX1-RUNX1T1 (p=0.027), and not attaining remission (p=0.016). On external validation, the risk score also predicted OS (p=0.019) in TCGA dataset. Conclusion: We identified and validated mitochondria-related DEGs with prognostic impact in pediatric AML and also developed a novel 3-gene based externally validated gene signature predictive of survival.

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Section: Discussionmentioning

confidence: 99%

Decoding mitochondrial genes in pediatric AML and development of a novel prognostic mitochondrial gene signature

Chaudhary

Ganguly

Palanichamy

et al. 2022

Preprint

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“…Here, patients with CLIC1-positive tumors have demonstrated worse overall survival compared to those with CLIC1-negative tumors [ 35 ]. CLIC1 expression is correlated to a poor prognosis not only in pancreatic cancer, but also in tumors as lung cancer [ 36 ], ovarian cancer, where CLIC1 upregulation was correlated to chemotherapy resistance [ 37 ], gallbladder, and gastric cancers [ 38 ], where it was found to promote cells proliferation via MAPK/AKT regulation [ 39 ] and facilitates the formation of tumor-associated fibroblasts [ 40 ]. In addition, CLIC1 protein upregulation correlates with the level of aggressiveness and metastatic potential of colorectal cancer cells [ 41 ], where it was demonstrated to regulate cell volume and ROS level.…”

Section: Clic1 During Chronic Allostasismentioning

confidence: 99%

Transmembrane Chloride Intracellular Channel 1 (tmCLIC1) as a Potential Biomarker for Personalized Medicine

Cianci

Verduci

2021

JPM

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Identification of potential pathological biomarkers has proved to be essential for understanding complex and fatal diseases, such as cancer and neurodegenerative diseases. Ion channels are involved in the maintenance of cellular homeostasis. Moreover, loss of function and aberrant expression of ion channels and transporters have been linked to various cancers, and to neurodegeneration. The Chloride Intracellular Channel 1 (CLIC1), CLIC1 is a metamorphic protein belonging to a partially unexplored protein superfamily, the CLICs. In homeostatic conditions, CLIC1 protein is expressed in cells as a cytosolic monomer. In pathological states, CLIC1 is specifically expressed as transmembrane chloride channel. In the following review, we trace the involvement of CLIC1 protein functions in physiological and in pathological conditions and assess its functionally active isoform as a potential target for future therapeutic strategies.

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“…In addition, it has been found that high CLIC1 expression may inhibit the proliferation of GC cells and promote their apoptosis, migration and invasion [57,67]. It has been shown that CLIC1 acts as a sensor and effector during oxidative stress [70] and affects the progression of various tumors through ROS regulation [69][70][71][72][73]. Previous studies have also shown that hypoxia-reoxygenation (H-R) may increase intracellular ROS levels to activate the MAPK/ERK pathway and that the CLIC1 protein participates in the migration of LOVO colon cancer cells by regulating the ROS/ERK pathway during H-R [69].…”

Section: Clic1 Participates In the Metastasis And Invasion Of Gc Cells By Regulating Hypoxia-reoxygenationinduced Intracellular Rosmentioning

confidence: 99%

Alteration and dysfunction of ion channels/transporters in a hypoxic microenvironment results in the development and progression of gastric cancer

Chen

Zhang

et al. 2021

Cell Oncol.

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Background Gastric cancer (GC) is one of the most common malignant cancers in the world and has only few treatment options and, concomitantly, a poor prognosis. It is generally accepted now that the tumor microenvironment, particularly that under hypoxia, plays an important role in cancer development. Hypoxia can regulate the energy metabolism and malignancy of tumor cells by inducing or altering various important factors, such as oxidative stress, reactive oxygen species (ROS), hypoxia-inducible factors (HIFs), autophagy and acidosis. In addition, altered expression and/or dysfunction of ion channels/transporters (ICTs) have been encountered in a variety of human tumors, including GC, and to play an important role in the processes of tumor cell proliferation, migration, invasion and apoptosis. Increasing evidence indicates that ICTs are at least partly involved in interactions between cancer cells and their hypoxic microenvironment. Here, we provide an overview of the different ICTs that regulate or are regulated by hypoxia in GC. Conclusions and perspectives Hypoxia is one of the major obstacles to cancer therapy. Regulating cellular responses and factors under hypoxia can inhibit GC. Similarly, altering the expression or activity of ICTs, such as the application of ion channel inhibitors, can slow down the growth and/or migration of GC cells. Since targeting the hypoxic microenvironment and/or ICTs may be a promising strategy for the treatment of GC, more attention should be paid to the interplay between ICTs and the development and progression of GC in such a microenvironment.

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The inhibition of chloride intracellular channel 1 enhances Ca2+ and reactive oxygen species signaling in A549 human lung cancer cells

Cited by 16 publications

References 60 publications

Decoding mitochondrial genes in pediatric AML and development of a novel prognostic mitochondrial gene signature

Decoding mitochondrial genes in pediatric AML and development of a novel prognostic mitochondrial gene signature

Transmembrane Chloride Intracellular Channel 1 (tmCLIC1) as a Potential Biomarker for Personalized Medicine

Alteration and dysfunction of ion channels/transporters in a hypoxic microenvironment results in the development and progression of gastric cancer

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