The role of myoglobin in epithelial cancers: Insights from transcriptomics.
Int J Mol Med
; 45(2): 385-400, 2020 Feb.
Article
em En
| MEDLINE
| ID: mdl-31894249
ABSTRACT
The muscleassociated respiratory protein myoglobin (MB) is expressed in multiple types of cancer, including breast and prostate tumors. In KaplanMeier analyses of the two tumor types, MB positivity is associated with favorable prognoses. Despite its wellcharacterized function in myocytes, the role of MB in cancer remains unclear. To study the impact of endogenous MB expression, small interfering RNA MBknockdown cells were engineered using breast, prostate and colon cancer cell lines (MDAMB468, LNCaP, DLD1), and their transcriptomes were investigated using RNASeq at different oxygen levels. In MBpositive cells, increased expression of glycolytic genes was observed, which was possibly mediated by a higher activity of hypoxiainducible factor 1α. In addition, the results of the gene set enrichment analysis suggested that MB contributed to fatty acid transport and turnover. MBpositive, wildtypep53 LNCaP cells also exhibited increased expression of p53 target genes involved in cell cycle checkpoint control and prevention of cell migration. MBpositive cells expressing mutant p53 exhibited upregulation of genes associated with prolonged cancer cell viability and motility. Therefore, it was hypothesized that these transcriptomic differences may result from MBmediated generation of nitric oxide or reactive oxygen species, thus employing established enzymatic activities of the globin. In summary, the transcriptome comparisons identified potential molecular functions of MB in carcinogenesis by highlighting the interaction of MB with key metabolic and regulatory processes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Neoplasias da Mama
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Neoplasias do Colo
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Mioglobina
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article