PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia

Chaudhary, Shilpi; Ganguly, Shuvadeep; Palanichamy, Jayanth Kumar; Singh, Archna; Bakhshi, Radhika; Jain, Ayushi; Chopra, Anita; Bakhshi, Sameer

doi:10.1016/j.mito.2021.03.013

Cited by 25 publications

(39 citation statements)

References 39 publications

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“…POLRMT is essential for mtDNA transcription and OXPHOS [ 12 , 23 , 24 ]. Recent studies have proposed POLRMT as a novel metabolic oncogene for human cancers [ 15 , 26 , 27 ]. Chaudhary et al reported that POLRMT is overexpressed in acute myeloid leukemia (AML), which is associated with increased mtDNA copy number and lower patients’ survival [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have proposed POLRMT as a novel metabolic oncogene for human cancers [ 15 , 26 , 27 ]. Chaudhary et al reported that POLRMT is overexpressed in acute myeloid leukemia (AML), which is associated with increased mtDNA copy number and lower patients’ survival [ 26 ]. Bralha et al reported that in AML cells shRNA-induced POLRMT silencing decreased mitochondrial gene expression, OXPHOS, and expressions of subunits of respiratory chain complexes, but increased cell death [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…IMT1 inhibited cancer cell growth in vitro and displayed a robust anti-tumor activity in xenografts of cancer cells [ 15 ]. These results implied that in cancer cells POLRMT blockage or silencing impaired mtDNA transcription and OXPHOS, thus inhibiting cancer growth [ 15 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

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The requirement of mitochondrial RNA polymerase for non-small cell lung cancer cell growth

et al. 2021

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POLRMT (RNA polymerase mitochondrial) is responsible for the transcription of mitochondrial genome encoding key components of oxidative phosphorylation. This process is important for cancer cell growth. The current study tested expression and potential functions of POLRMT in non-small cell lung cancer (NSCLC). TCGA cohorts and the results from the local lung cancer tissues showed that POLRMT is overexpressed in human lung cancer tissues. In both primary human NSCLC cells and A549 cells, POLRMT silencing (by targeted lentiviral shRNAs) or knockout (through CRSIPR/Cas9 gene editing method) potently inhibited cell viability, proliferation, migration, and invasion, and induced apoptosis activation. On the contrast, ectopic overexpression of POLRMT using a lentiviral construct accelerated cell proliferation and migration in NSCLC cells. The mtDNA contents, mRNA levels of mitochondrial transcripts, and subunits of respiratory chain complexes, as well as S6 phosphorylation, were decreased in POLRMT-silenced or -knockout NSCLC cells, but increased after ectopic POLRMT overexpression. In vivo, intratumoral injection of POLRMT shRNA adeno-associated virus (AAV) potently inhibited NSCLC xenograft growth in severe combined immune deficiency mice. The mtDNA contents, mRNA levels of mitochondria respiratory chain complex subunits, and S6 phosphorylation were decreased in POLRMT shRNA AAV-injected NSCLC xenograft tissues. These results show that POLRMT is a novel and important oncogene required for NSCLC cell growth in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The requirement of mitochondrial RNA polymerase for non-small cell lung cancer cell growth

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…POLRMT is essential for mtDNA transcription and OXPHOS [ 26 – 28 ], represents as a novel therapeutic target for human cancer [ 15 , 18 , 29 ]. POLRMT overexpression in AML is associated increased mtDNA copy number and lower overall survival [ 29 ]. In AML cells, POLRMT knockdown by shRNA reduced mitochondrial gene expression and inhibited OXPHOS and expression of respiratory chain complex subunits, causing significant cell death [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of mitochondrial RNA polymerase as a potential therapeutic target of osteosarcoma

et al. 2021

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POLRMT (RNA polymerase mitochondrial) is essential for transcription of mitochondrial genome encoding components of oxidative phosphorylation process. The current study tested POLRMT expression and its potential function in osteosarcoma (OS). The Cancer Genome Atlas (TCGA) cohorts and Gene Expression Profiling Interactive Analysis (GEPIA) database both show that POLRMT transcripts are elevated in OS tissues. In addition, POLRMT mRNA and protein levels were upregulated in local OS tissues as well as in established and primary human OS cells. In different OS cells, shRNA-induced stable knockdown of POLRMT decreased cell viability, proliferation, migration, and invasion, whiling inducing apoptosis activation. CRISPR/Cas9-induced POLRMT knockout induced potent anti-OS cell activity as well. Conversely, in primary OS cells ectopic POLRMT overexpression accelerated cell proliferation and migration. In vivo, intratumoral injection of adeno-associated virus-packed POLRMT shRNA potently inhibited U2OS xenograft growth in nude mice. Importantly, levels of mitochondrial DNA, mitochondrial transcripts and expression of respiratory chain complex subunits were significantly decreased in U2OS xenografts with POLRMT shRNA virus injection. Together, POLRMT is overexpressed in human OS, promoting cell growth in vitro and in vivo. POLRMT could be a novel therapeutic target for OS.

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Transcriptome analysis of porcine oocytes during postovulatory aging

Yu,

Peng,

Cai

et al. 2024

Theriogenology

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PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia

Cited by 25 publications

References 39 publications

The requirement of mitochondrial RNA polymerase for non-small cell lung cancer cell growth

The requirement of mitochondrial RNA polymerase for non-small cell lung cancer cell growth

Identification of mitochondrial RNA polymerase as a potential therapeutic target of osteosarcoma

Transcriptome analysis of porcine oocytes during postovulatory aging

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