Inhibition of mitochondrial carrier homolog 2 (MTCH2) suppresses tumor invasion and enhances sensitivity to temozolomide in malignant glioma

Yuan, Qiuyun; Yang, Wanchun; Zhang, Shuxin; Li, Tengfei; Zuo, Mingrong; Zhou, Xingwang; Li, Junhong; Li, Mao; Xia, Xiaoqiang; Chen, Mina; Liu, Yan‐Hui

doi:10.1186/s10020-020-00261-4

Cited by 13 publications

(7 citation statements)

References 41 publications

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“…MTCH2 expression has been associated with several cancers [ 46 , 47 ]. Recently, Yuan et al explained the oncogenic role of altered MTCH2 expression in malignant glioma [ 48 ]. MTCH2 , present on the outer mitochondrial membrane, plays a crucial role in chemoresistance and tumor migration in gliomas.…”

Section: Discussionmentioning

confidence: 99%

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Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing

et al. 2023

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Background: Glioblastoma poses an inevitable threat to patients despite aggressive therapy regimes. It displays a great level of molecular heterogeneity and numerous substitutions in several genes have been documented. Next-generation sequencing techniques have identified various molecular signatures that have led to a better understanding of the molecular pathogenesis of glioblastoma. In this limited study, we sought to identify genetic variants in a small number of rare patients with aggressive glioblastoma. Methods: Five tumor tissue samples were isolated from four patients with rapidly growing glioblastoma. Genomic DNA was isolated and whole exome sequencing was used to study protein-coding regions. Generated FASTQ files were analyzed and variants were called for each sample. Variants were prioritized with different approaches and functional annotation was applied for the detrimental variants. Results: A total of 49,780 somatic variants were identified in the five glioblastoma samples studied, with the majority as missense substitutions. The top ten genes with the highest number of substitutions were MUC3A, MUC4, MUC6, OR4C5, PDE4DIP, AHNAK2, OR4C3, ZNF806, TTN, and RP1L1. Notably, variant prioritization after annotation indicated that the MTCH2 (Chr11: 47647265 A>G) gene sequence change was putative deleterious in all of the aggressive tumor samples. Conclusion: The MTCH2 (Chr11: 47647265 A>G) gene substitution was identified as putative deleterious in highly aggressive glioblastomas, which merits further investigation. Moreover, a high tumor mutation burden was observed, with a signature of the highest substitutions in MUC3A, MUC4, MUC6, OR4C5, PDE4DIP, AHNAK2, OR4C3, ZNF806, TTN, and RP1L1 genes. The findings provide critical, initial data for the further rational design of genetic screening and diagnostic approaches against aggressive glioblastoma.

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Section: Discussionmentioning

confidence: 99%

“…In human glioma cells, MTCH2 knockdown increases the mitochondrial OXPHOs, which subsequently enhances oxidative damage in glioma cells. Abrogation of MTCH2 gene expression attenuated the invasive property of glioma cells and enhanced Temozolomide sensitivity via down-regulation of the AKT signaling pathway [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing

et al. 2023

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“…In vitro studies indicate that Bcl2 proteins may play important mitochondrial dynamics housekeeping roles ( Karbowski et al, 2006 ). Mitochondrial carrier homologue 2 (MTCH2) is known as a regulator of mitochondrial metabolism and apoptosis as it is a repressor of mitochondrial OXPHOS ( Yuan et al, 2021 ). However, in vitro studies involving embryonic stem cells (ESCs) show that MTCH2 may serve as a novel regulator of mitochondrial fusion, because knockout of MTCH2 from ESCs results in failure of mitochondria to elongate ( Bahat et al, 2018 ).…”

Section: Regulation Of Mitochondrial Fusion and Fissionmentioning

confidence: 99%

Mitochondrial dynamics involves molecular and mechanical events in motility, fusion and fission

Green

Hossain²,

Eckmann³

2022

Front. Cell Dev. Biol.

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Mitochondria are cell organelles that play pivotal roles in maintaining cell survival, cellular metabolic homeostasis, and cell death. Mitochondria are highly dynamic entities which undergo fusion and fission, and have been shown to be very motile in vivo in neurons and in vitro in multiple cell lines. Fusion and fission are essential for maintaining mitochondrial homeostasis through control of morphology, content exchange, inheritance of mitochondria, maintenance of mitochondrial DNA, and removal of damaged mitochondria by autophagy. Mitochondrial motility occurs through mechanical and molecular mechanisms which translocate mitochondria to sites of high energy demand. Motility also plays an important role in intracellular signaling. Here, we review key features that mediate mitochondrial dynamics and explore methods to advance the study of mitochondrial motility as well as mitochondrial dynamics-related diseases and mitochondrial-targeted therapeutics.

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“…Transwell assay was performed as described in our previous study (Yuan et al 2021). For cells invasion assay, brie y, the 8-µm pore chambers (Corning, USA) were precoated with 50 µL Matrigel (Matrigel: precooling DMEM = 1:4) in a 24-well plate and incubated at 37°C.…”

Section: Cell Migration and Invasion Assaymentioning

confidence: 99%

Integrated Analysis Identifies MEOX2 as a Malignant Driver and Prognostic Biomarker in Brain Glioma

Sun

Yang

et al. 2022

Preprint

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Purpose: Glioma is a common type of malignant tumor in the brain, of which glioblastoma (GBM) is the most aggressive and lethal form. Despite current progress in the clinical treatment, the prognosis of GBM is still not satisfied, mainly due to the genomic alternations and complicated gene regulatory network. MEOX2 was originally identified as a homeobox transcriptional factor, that was reported to play a role in several types of cancers. However, the expression pattern and biological functions of MEOX2 in glioma are not well elucidated. This study aims to clarify the role of MEOX2 in glioma.Methods: Bioinformatic analysis from TCGA and CGGA databases was used to investigate the correlation of MEOX2 with glioma malignancy and clinical prognosis. The expression of MEOX2 was confirmed from clinical samples by qPCR and western blot. Lentivirus-mediated MEOX2 overexpression and knockdown were employed to investigate the biological functions of MEOX2 in glioma malignant behaviors. RNA-seq and signaling investigations were performed to reveal the molecular mechanisms.Results: Bioinformatic data from public databases and our cohort showed that MEOX2 expression was highly associated with glioma malignancy and could predict the poor prognosis. MEOX2 positively regulates glioma cell proliferation, migration/invasion and chemoresistance to temozolomide. Mechanistically, MEOX2 regulates gene profiles related to PI3K/AKT/mTORC1 pathways and thus promotes glioma malignancy.Conclusion: Our work identifies the novel function of MEOX2 in gliomas, and provides a potential target for glioma prognosis and clinical interventions.

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Inhibition of mitochondrial carrier homolog 2 (MTCH2) suppresses tumor invasion and enhances sensitivity to temozolomide in malignant glioma

Cited by 13 publications

References 41 publications

Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing

Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing

Mitochondrial dynamics involves molecular and mechanical events in motility, fusion and fission

Integrated Analysis Identifies MEOX2 as a Malignant Driver and Prognostic Biomarker in Brain Glioma

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