Inhibition of Mitochondrial Carrier Homolog 2 (MTCH2) Suppresses Tumor Invasion and Enhances Sensitivity to Temozolomide in Malignant Glioma
Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma.
Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy.
Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling.
Conclusion: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.
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Due to technical limitations, the tables are only available as a download in the supplemental files section.
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Posted 31 Dec, 2020
On 28 Jan, 2021
Invitations sent on 16 Dec, 2020
On 16 Dec, 2020
Received 16 Dec, 2020
On 16 Dec, 2020
On 10 Dec, 2020
On 10 Dec, 2020
On 10 Dec, 2020
On 25 Nov, 2020
Received 25 Nov, 2020
Invitations sent on 23 Nov, 2020
On 23 Nov, 2020
On 17 Nov, 2020
On 17 Nov, 2020
On 17 Nov, 2020
On 09 Sep, 2020
Received 29 Aug, 2020
Received 16 Aug, 2020
On 12 Aug, 2020
On 11 Aug, 2020
On 11 Aug, 2020
On 10 Aug, 2020
Invitations sent on 10 Aug, 2020
On 09 Aug, 2020
On 06 Aug, 2020
On 03 Aug, 2020
Inhibition of Mitochondrial Carrier Homolog 2 (MTCH2) Suppresses Tumor Invasion and Enhances Sensitivity to Temozolomide in Malignant Glioma
Posted 31 Dec, 2020
On 28 Jan, 2021
Invitations sent on 16 Dec, 2020
On 16 Dec, 2020
Received 16 Dec, 2020
On 16 Dec, 2020
On 10 Dec, 2020
On 10 Dec, 2020
On 10 Dec, 2020
On 25 Nov, 2020
Received 25 Nov, 2020
Invitations sent on 23 Nov, 2020
On 23 Nov, 2020
On 17 Nov, 2020
On 17 Nov, 2020
On 17 Nov, 2020
On 09 Sep, 2020
Received 29 Aug, 2020
Received 16 Aug, 2020
On 12 Aug, 2020
On 11 Aug, 2020
On 11 Aug, 2020
On 10 Aug, 2020
Invitations sent on 10 Aug, 2020
On 09 Aug, 2020
On 06 Aug, 2020
On 03 Aug, 2020
Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma.
Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy.
Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling.
Conclusion: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Due to technical limitations, the tables are only available as a download in the supplemental files section.