Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in human lung adenocarcinoma

Cheng, Chi‐Feng; Wooten, Joshua S.; Gibbs, Zane A.; McGlynn, Kathleen; Mishra, Prashant; Whitehurst, Angelique W.

doi:10.7554/elife.58108

Cited by 34 publications

(30 citation statements)

References 54 publications

(78 reference statements)

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“…Similar to our results, a previous study reported that FTO expression was positively related to dextrose oxidation rates and levels of genes related to oxidative phosphorylation in skeletal muscle [47]. It has been shown that oxidative phosphorylation plays significant roles in lung cancer proliferation, invasion, metastasis, and drug resistance [48][49][50]. erefore, it is likely that genetic alterations of FTO regulate the progression of NSCLC by affecting cellular oxidative phosphorylation levels.…”

Section: Discussionsupporting

confidence: 90%

Gene Characteristics and Prognostic Values of m6A RNA Methylation Regulators in Nonsmall Cell Lung Cancer

Chen

Liu

et al. 2021

Journal of Healthcare Engineering

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Background. N6-methyladenosine (m6A) is the most common internal modiﬁcation present in mRNAs and long noncoding RNAs (lncRNAs), associated with tumorigenesis and cancer progression. However, little is known about the roles of m6A and its regulatory genes in nonsmall cell lung cancer (NSCLC). Here, we systematically explored the roles and prognostic significance of m6A-associated regulatory genes in NSCLC. Methods. The copy number variation (CNV), mutation, mRNA expression data, and corresponding clinical pathology information of 1057 NSCLC patients were downloaded from the cancer genome atlas (TCGA) database. The gain and loss levels of CNVs were determined by utilizing segmentation analysis and GISTIC algorithm. The GSEA was conducted to explore the functions related to different levels of m6A regulatory genes. Logrank test was utilized to assess the prognostic significance of m6A-related gene’s CNV. Results. The genetic alterations of ten m6A-associated regulators were identified in 102 independent NSCLC samples and significantly related to advanced tumor stage. Deletions or shallow deletions corresponded to lower mRNA expression while copy number gains or amplifications were related to increased mRNA expression of m6A regulatory genes. Survival analysis showed the patients with copy number loss of FTO with worse disease-free survival (DFS) or overall survival (OS). Besides, copy number loss of YTHDC2 was also with poor OS for NSCLC patients. Moreover, high FTO expression was significantly associated with oxidative phosphorylation, translation, and metabolism of mRNA. Conclusion. Our findings provide novel insight for better understanding of the roles of m6A regulators and RNA epigenetic modification in the pathogenesis of NSCLC.

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Section: Discussionsupporting

confidence: 90%

Gene Characteristics and Prognostic Values of m6A RNA Methylation Regulators in Nonsmall Cell Lung Cancer

Chen

Liu

et al. 2021

Journal of Healthcare Engineering

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“…As a consequence, subsequently acquired (pseudo)meiotic functions may help the cancer cells to disturb normal cell cycle regulation and DNA repair mechanisms in order to evade checkpoints and apoptosis [ 10 ]. Indeed, and consistently with previous reports on CT genes [ 38 ], the expression of the meiosis specific gene HORMAD1 [ 39 , 40 ], the MAGE-A gene family [ 41 ], and the sperm specific cytochrome c oxidase COX6B2 [ 42 , 43 ], we found that a high GC signature score correlates with poor prognosis in lung adenocarcinoma.…”

Section: Discussionsupporting

confidence: 91%

Tumors Widely Express Hundreds of Embryonic Germline Genes

Bruggeman

Irie

Lodder

et al. 2020

Cancers

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We have recently described a class of 756 genes that are widely expressed in cancers, but are normally restricted to adult germ cells, referred to as germ cell cancer genes (GC genes). We hypothesized that carcinogenesis involves the reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17,382 samples from 54 healthy somatic tissues (GTEx) and 11,003 samples from 33 tumor types (TCGA), and identified 672 GC genes, expanding the known GC gene pool by 387 genes (51%). We found that GC genes are expressed in clusters that are often expressed in multiple tumor types. Moreover, the amount of GC gene expression correlates with poor survival in patients with lung adenocarcinoma. As GC genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC genes and may preserve fertility. We anticipate that our extended GC dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development.

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“…[ 49 ] COX6B2 and NDUFB9 are the components in the mitochondrial electron transport chain. [ 50,51 ] GSN is located to the mitochondrial outer membrane and protects cell from death. [ 52,53 ] Mitochondria not only are the powerhouse of cells but also play essential roles in iron homeostasis, lipid metabolism and cell death signaling.…”

Section: Resultsmentioning

confidence: 99%

RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment

et al. 2021

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Nanosafety is a major concern for nanotechnology development. Evaluation of the transcriptome and the DNA methylome is proposed for nanosafety assessments. RNA m6A modification plays a crucial role in development, disease, and cell fate determination through regulating RNA stability and decay. Here, since black phosphorus quantum dots (BPQDs), among many other types of QDs, increase the global m6A level and decrease the demethylase ALKBH5 level in lung cells, the epitranscriptome is taken into consideration for the first time to evaluate nanosafety. Both the transcriptome and m6A epitranscriptome analyses show that BPQDs alter many biological processes, such as the response to selenium ions and the lipoxygenase pathway, indicating possible ferroptosis activation. The results further show that BPQDs cause lipid peroxidation, mitochondrial dysfunction, and iron overload. Recognition of these modified mRNAs by YTHDF2 leads to mRNAs’ decay and eventually ferroptosis. This study shows that RNA m6A modification not only is a more sophisticated indicator for nanosafety assessment but also provides novel insight into the role of RNA m6A in regulating BPQD‐induced ferroptosis, which may be broadly applicable to understanding the functions of RNA m6A under stress.

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Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in human lung adenocarcinoma

Cited by 34 publications

References 54 publications

Gene Characteristics and Prognostic Values of m6A RNA Methylation Regulators in Nonsmall Cell Lung Cancer

Gene Characteristics and Prognostic Values of m6A RNA Methylation Regulators in Nonsmall Cell Lung Cancer

Tumors Widely Express Hundreds of Embryonic Germline Genes

RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment

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