Loss of ferrochelatase is protective against colon cancer cells: ferrochelatase a possible regulator of the long noncoding RNA H19
Safi, Mohsen-Kanson, Nemer, Dekmak, Rubeiz, El-Sabban, Nassar, Eid, Abbas, Kibbi, Kurban (2019) Loss of ferrochelatase is protective against colon cancer cells: ferrochelatase a possible regulator of the long noncoding RNA H19 J Gastrointest Oncol (IF: 2.1) 10(5) 859-868
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Abstract
Ferrochelatase (FECH) is the last enzyme of the heme biosynthesis pathway. Deficiency in FECH was associated with many diseases, including protoporphyria. Correlation studies showed that variations of FECH expression was detected in human carcinomas and more specifically in colon cancer. Nevertheless, the potential role of FECH in colon cancer carcinogenesis in vitro was not depicted yet.A small interfering RNA (siRNA) was used to knockdown FECH in human Caco-2 colon cancer cells. The effect of FECH down-regulation on the cellular proliferation, the migration and the expression of target genes was assessed in cancer cells and compared to human normal fibroblasts.Following FECH down-regulation, our results demonstrated that the proliferation of Caco-2 cells was not affected. Furthermore, the migration of cancer and normal cells was affected, only when an additional stress factor (H2O2) was applied to the medium. The expression of twist, snail, hypoxia induced factor (HIF-1α) and vascular endothelial growth factor (VEGF) was reduced in Caco-2 cells. Conversely, VEGF and HIF-1α expression were upregulated by up to 2 folds in control fibroblasts. Interestingly, the pro-carcinogenic long noncoding RNA (LncRNA) H19 was 70% down-regulated in Caco-2 cells upon FECH down regulation whereas no effect was observed in normal fibroblasts.In conclusion, we showed that loss of FECH is protective against colon cancer tumorigenesis in vitro and this effect could possibly be mediated through inhibition of H19.2019 Journal of Gastrointestinal Oncology. All rights reserved.
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776811http://www.ncbi.nlm.nih.gov/pubmed/31602323
http://dx.doi.org/10.21037/jgo.2019.03.09
