Diabetes-mediated promotion of colon mucosa carcinogenesis is associated with mitochondrial dysfunction
Fuente:
Zenodo
Salvato in:
| Autori principali: | , , , , , , , , , , , , , , , , , |
|---|---|
| Natura: | Recurso digital |
| Lingua: | inglese |
| Pubblicazione: |
Zenodo
2019
|
| Soggetti: | |
| Accesso online: | |
| Tags: |
Aggiungi Tag
Nessun Tag, puoi essere il primo ad aggiungerne!!
|
| _version_ | 1866901577556557824 |
|---|---|
| author | del Puerto Nevado, Laura Santiago Hernandez, Aránzazu Sonia Solanes Casado González, Nieves Marta Ricole Vila Corton, Marta Prieto, Isabel Mas, Sebastian Sanz, Ana Belen aguilera, oscar Gomez-Guerrero, Carmen Ayuso, Carmen Ortiz Arduan, Alberto Rojo, Federico Egido, Jesus J, Garcia-Foncillas Minguez, Pablo Alvarez-Llamas, Gloria |
| author_facet | del Puerto Nevado, Laura Santiago Hernandez, Aránzazu Sonia Solanes Casado González, Nieves Marta Ricole Vila Corton, Marta Prieto, Isabel Mas, Sebastian Sanz, Ana Belen aguilera, oscar Gomez-Guerrero, Carmen Ayuso, Carmen Ortiz Arduan, Alberto Rojo, Federico Egido, Jesus J, Garcia-Foncillas Minguez, Pablo Alvarez-Llamas, Gloria |
| contents | <p>Type 2 diabetes mellitus (T2DM) has been associated with an increased risk<br>of cancer, including colon cancer (CC). However, we recently reported no<br>influence of T2DM on CC prognosis, suggesting that any effect might be at<br>the early stages of tumor development. We hypothesized that T2DM may<br>create an environment in the healthy tissue, which acts as a carcinogenesis<br>driver in agreement with the field of cancerization concept. Here, we focused<br>on early carcinogenesis by analyzing paired tumor and normal colonic<br>mucosa samples from the same patients. The proteome of CC and paired<br>mucosa was quantitatively analyzed in 28 individuals (12 diabetics and 16<br>nondiabetics) by mass spectrometry with isobaric labeling. Out of 3076 identified<br>proteins, 425 were differentially expressed at the tumor in diabetics<br>compared with nondiabetics. In the adjacent mucosa, 143 proteins were differentially<br>expressed in diabetics and nondiabetics. An enrichment analysis<br>of this signature pointed to mitochondria, ribosome, and translation. Only<br>six proteins were upregulated by diabetes both in tumor and mucosa, of<br>which five were mitochondrial proteins. Differential expression in diabetic<br>versus nondiabetic mucosa was confirmed for MRPL53, MRPL18, and<br>TIMM8B. Higher levels of MRPL18, TIMM8B, and EIF1A were also found<br>in normal colon epithelial cells exposed to high-glucose conditions. We conclude<br>that T2DM is associated with specific molecular changes in the normal<br>mucosa of CC patients, consistent with field of cancerization in a diabetic<br>environment. The mitochondrial protein signature identifies a potential therapeutic<br>target that could underlie the higher risk of CC in diabetics.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_18772534 |
| institution | Zenodo |
| language | eng |
| publishDate | 2019 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Diabetes-mediated promotion of colon mucosa carcinogenesis is associated with mitochondrial dysfunction del Puerto Nevado, Laura Santiago Hernandez, Aránzazu Sonia Solanes Casado González, Nieves Marta Ricole Vila Corton, Marta Prieto, Isabel Mas, Sebastian Sanz, Ana Belen aguilera, oscar Gomez-Guerrero, Carmen Ayuso, Carmen Ortiz Arduan, Alberto Rojo, Federico Egido, Jesus J, Garcia-Foncillas Minguez, Pablo Alvarez-Llamas, Gloria colon cancer; diabetes; field of cancerization; mitochondria; proteomics <p>Type 2 diabetes mellitus (T2DM) has been associated with an increased risk<br>of cancer, including colon cancer (CC). However, we recently reported no<br>influence of T2DM on CC prognosis, suggesting that any effect might be at<br>the early stages of tumor development. We hypothesized that T2DM may<br>create an environment in the healthy tissue, which acts as a carcinogenesis<br>driver in agreement with the field of cancerization concept. Here, we focused<br>on early carcinogenesis by analyzing paired tumor and normal colonic<br>mucosa samples from the same patients. The proteome of CC and paired<br>mucosa was quantitatively analyzed in 28 individuals (12 diabetics and 16<br>nondiabetics) by mass spectrometry with isobaric labeling. Out of 3076 identified<br>proteins, 425 were differentially expressed at the tumor in diabetics<br>compared with nondiabetics. In the adjacent mucosa, 143 proteins were differentially<br>expressed in diabetics and nondiabetics. An enrichment analysis<br>of this signature pointed to mitochondria, ribosome, and translation. Only<br>six proteins were upregulated by diabetes both in tumor and mucosa, of<br>which five were mitochondrial proteins. Differential expression in diabetic<br>versus nondiabetic mucosa was confirmed for MRPL53, MRPL18, and<br>TIMM8B. Higher levels of MRPL18, TIMM8B, and EIF1A were also found<br>in normal colon epithelial cells exposed to high-glucose conditions. We conclude<br>that T2DM is associated with specific molecular changes in the normal<br>mucosa of CC patients, consistent with field of cancerization in a diabetic<br>environment. The mitochondrial protein signature identifies a potential therapeutic<br>target that could underlie the higher risk of CC in diabetics.</p> |
| title | Diabetes-mediated promotion of colon mucosa carcinogenesis is associated with mitochondrial dysfunction |
| topic | colon cancer; diabetes; field of cancerization; mitochondria; proteomics |
| url | https://doi.org/10.5281/zenodo.18772534 |