MNRR1 is a driver of ovarian cancer progression

Chehade, Hussein; Purandare, Neeraja; Fox, Alexandra; Adzibolosu, Nicholas; Jayee, Shawn; Singh, Aryan; Tedja, Roslyn; Gogoi, Radhika; Aras, Siddhesh; Grossman, Lawrence I.; Mor, Gil; Alvero, Ayesha B.

doi:10.1016/j.tranon.2023.101623

Cited by 4 publications

(2 citation statements)

References 32 publications

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“…RNA sequencing: RNA sequencing of CTGF knockout (KO) and wild-type (WT) R182 cells were performed by GENEWIZ LLC (South Plainfield, NJ, USA) as described previously [18]. Differential gene expression analysis comparing R182-CTGFKO cells to WT R182-WT cells was performed by GENEWIZ LLC using the DESeq2 package [19].…”

Section: Methodsmentioning

confidence: 99%

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

Gogoi,

Galoforo,

Fox

et al. 2023

Cancers

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Background: Epithelial–mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between the epithelial and mesenchymal stage is essential for tissue homeostasis. Many of the genes promoting mesenchymal transformation have been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify the genes responsible for maintaining the epithelial phenotype and inhibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expression was determined via qPCR and Western blot analysis. The knockout of CTGF was completed using the CTGF sgRNA CRISPR/CAS9. The tumorigenic potential was determined using NCG mice. Results: The knockout of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as anoikis resistance, cytoskeleton remodeling, increased cell stiffness, and the acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with the early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for the conservation of epithelial structure and function. These findings provide a new window into understanding the early stages of mesenchymal transformation.

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Section: Methodsmentioning

confidence: 99%

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

Gogoi,

Galoforo,

Fox

et al. 2023

Cancers

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“…The significance of CHCHD2 extends to various diseases. It has been implicated in cancers (i.e ., induction) [ 32 , 33 ], Parkinson’s disease (i.e. , mutations) [ 34 ] and mitochondrial encephalomyopathy (i.e ., repression).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity

Kim,

Kwon,

Kim

et al. 2024

Cell. Mol. Life Sci.

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During in vitro culture, human pluripotent stem cells (hPSCs) often acquire survival advantages characterized by decreased susceptibility to mitochondrial cell death, known as “culture adaptation.” This adaptation is associated with genetic and epigenetic abnormalities, including TP53 mutations, copy number variations, trisomy, and methylation changes. Understanding the molecular mechanisms underlying this acquired survival advantage is crucial for safe hPSC-based cell therapies. Through transcriptome and methylome analysis, we discovered that the epigenetic repression of CHCHD2, a mitochondrial protein, is a common occurrence during in vitro culture using enzymatic dissociation. We confirmed this finding through genetic perturbation and reconstitution experiments in normal human embryonic stem cells (hESCs). Loss of CHCHD2 expression conferred resistance to single cell dissociation-induced cell death, a common stress encountered during in vitro culture. Importantly, we found that the downregulation of CHCHD2 significantly attenuates the activity of Rho-associated protein kinase (ROCK), which is responsible for inducing single cell death in hESCs. This suggests that hESCs may survive routine enzyme-based cell dissociation by downregulating CHCHD2 and thereby attenuating ROCK activity. These findings provide insights into the mechanisms by which hPSCs acquire survival advantages and adapt to in vitro culture conditions.

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ScHGSC-IGDC: Identifying genes with differential correlations of high-grade serous ovarian cancer based on single-cell RNA sequencing analysis

Li,

Wang,

Zheng

et al. 2024

Heliyon

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MNRR1 is a driver of ovarian cancer progression

Cited by 4 publications

References 32 publications

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity

ScHGSC-IGDC: Identifying genes with differential correlations of high-grade serous ovarian cancer based on single-cell RNA sequencing analysis

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