Systematic Elucidation of the Aneuploidy Landscape and Identification of Aneuploidy Driver Genes in Prostate Cancer

Peng, Yun; Song, Yuxuan; Wang, Haitao

doi:10.3389/fcell.2021.723466

Cited by 4 publications

(3 citation statements)

References 107 publications

(122 reference statements)

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“…Through Kaplan-Meier plotter analysis, significant differences were observed in the survival curves between patients with high and low expression of FAXDC2. This analysis confirmed that FAXDC2 expression is downregulated in prostate cancer and neuroblastoma and low expression of FAXDC2 is indicative of an unfavorable prognosis for these diseases (24,25), in accordance with the experimental findings of the present study.…”

Section: Discussionsupporting

confidence: 92%

“…Controlling the content of cholesterol and sphingomyelin can artificially achieve the dynamic remodeling of lipid rafts ( 22 , 23 ), thereby changing the transduction properties of intracellular signals. It has been reported that the expression of FAXDC2 is downregulated in prostate cancer and neuroblastoma and low expression of FAXDC2 is an unfavorable factor for disease prognosis ( 24 , 25 ). Another study has shown that FAXDC2 can regulate macrophage differentiation by regulating ERK signaling-related mechanisms ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

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FAXDC2 inhibits the proliferation and invasion of human liver cancer HepG2 cells

Peng,

Xu,

Zhang

et al. 2023

Exp Ther Med

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The reprogramming of lipid metabolism serves an important role in occurrence and development of liver cancer. Fatty acid hydroxylase domain containing 2 (FAXDC2) is a hydroxylase involved in the synthesis of cholesterol and sphingomyelin and downregulated in various types of cancer. There are no reports on the relationship between FAXDC2 and liver carcinogenesis. The present study used multiple portals and publicly available tools to explore its correlation with liver cancer. The results showed that the expression of FAXDC2 decreased in liver cancer and the methylation level near the promoter increased. Patients with liver cancer and with low expression of FAXDC2 had a poor prognosis. Gain of function and loss of function strategies were performed to evaluate its roles in liver cancer cells. CCK-8 assay showed that overexpression of FAXDC2 inhibited the viability of liver cancer cells (HepG2). Flow cytometry analysis indicated that HepG2 cells with overexpressing FAXDC2 showed an S phase arrest, associated with cyclin-dependent kinase 2 decreased. Transwell experiments showed that increasing FAXDC2 inhibited HepG2 cell invasion ability, accompanied by the upregulation of E-cadherin. Notably, knockdown of FAXDC2 had no significant effect on cell cycle and invasion functions. Based on the cBioPortal platform, FAXDC2 was predicted to closely correlate to the ERK signal in tumorigenesis. Western blotting results showed that overexpression of FAXDC2 decreased the phosphorylation level of ERK in liver cancer cells. The present study first identified FAXDC2 as a liver cancer suppressor, which might inhibit the proliferation and invasion of liver cancer cells through the mechanism associated with ERK signaling. The present study provided a possible new target for the diagnosis and treatment of liver cancer.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

FAXDC2 inhibits the proliferation and invasion of human liver cancer HepG2 cells

Peng,

Xu,

Zhang

et al. 2023

Exp Ther Med

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“…Elevated miRNAs as a direct or indirect consequence of impaired tRNA processing correlated with reduced mRNAs involved in mitochondrial function and potentiation of inflammation and cell growth in the KO and A537T mutant mice compared with controls (Appendix Fig S10 A), such as miR‐10a‐5p that correlated with reduced the expression of the mitochondrial thiosulfate sulphur transferase ( Tst ; Fig 6E and F ). Reduced miRNAs such as miR‐122‐5p and miR‐383‐5p/miR‐338‐3p correlated with an increase of mRNAs involved in cell transformation ( Gldc ; Liu et al , 2021 ), inhibition of apoptosis ( Bcl2 ), prostate tumorigenesis ( Trp63 ; Pignon et al , 2013 ) and hypoxia ( Hif3a ; Peng et al , 2022 ) in the KO and A537T mutant mice compared with controls (Fig 6E and F ).…”

Section: Resultsmentioning

confidence: 88%

Multi‐omic profiling reveals an RNA processing rheostat that predisposes to prostate cancer

et al. 2023

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Prostate cancer is the most commonly diagnosed malignancy and the third leading cause of cancer deaths. GWAS have identified variants associated with prostate cancer susceptibility; however, mechanistic and functional validation of these mutations is lacking. We used CRISPR‐Cas9 genome editing to introduce a missense variant identified in the ELAC2 gene, which encodes a dually localised nuclear and mitochondrial RNA processing enzyme, into the mouse Elac2 gene as well as to generate a prostate‐specific knockout of Elac2. These mutations caused enlargement and inflammation of the prostate and nodule formation. The Elac2 variant or knockout mice on the background of the transgenic adenocarcinoma of the mouse prostate (TRAMP) model show that Elac2 mutation with a secondary genetic insult exacerbated the onset and progression of prostate cancer. Multiomic profiling revealed defects in energy metabolism that activated proinflammatory and tumorigenic pathways as a consequence of impaired noncoding RNA processing and reduced protein synthesis. Our physiologically relevant models show that the ELAC2 variant is a predisposing factor for prostate cancer and identify changes that underlie the pathogenesis of this cancer.

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Analysis of the accumulation of homozygosity regions in chickens of the Pushkin breed using data from whole genome genotyping

Дементьева

Shcherbakov

Митрофанова

et al. 2022

Ecological genetics

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BACKGROUND: The search for genetic factors influencing the formation of the productive qualities of new breeding forms and populations of chickens is an important direction in the study of animal genomes. The knowledge gained can be in demand in projects to create modern domestic highly productive poultry lines. AIM: To conduct a comparative analysis of the localization of homozygous regions on chicken chromosomes in representatives of four breeds from the Genetic Collection of Rare and Endangered Breeds of Chickens to identify traces of selection and search for genes associated with productive traits. MATERIALS AND METHODS: Based on the bioinformatic analysis of 42275 SNP markers identified using the Illumina Chicken 60K SNP iSelect BeadChip microchip, data were obtained on the distribution of homozygous regions of four populations of chickens at the Genetic Collection of Rare and Endangered Breeds of Chickens (VNIIGRZH, St. Petersburg): Pushkinskaya (n = 20), Cornish (n = 22), Black-and-White Australorp (n = 20), Russian White (n = 23). RESULTS AND CONCLUSIONS: In chickens of the Pushkin breed, the observed heterozygosity was 0.372 0.004, which is higher than in other populations. According to the inbreeding index, based on the analysis of homozygous regions, the maximum level was found in Cornish chickens. For the Pushkin breed, the accumulation of homozygous regions on chromosomes 1, 2, 6, 8 was noted. The genes annotated in these loci are evidence of intensive selection.

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Systematic Elucidation of the Aneuploidy Landscape and Identification of Aneuploidy Driver Genes in Prostate Cancer

Cited by 4 publications

References 107 publications

FAXDC2 inhibits the proliferation and invasion of human liver cancer HepG2 cells

FAXDC2 inhibits the proliferation and invasion of human liver cancer HepG2 cells

Multi‐omic profiling reveals an RNA processing rheostat that predisposes to prostate cancer

Analysis of the accumulation of homozygosity regions in chickens of the Pushkin breed using data from whole genome genotyping

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