铁螯合酶缺失对结肠癌细胞具有保护作用：铁螯合酶可能是长链非编码RNA H19的一种调节因子。
Loss of ferrochelatase is protective against colon cancer cells: ferrochelatase a possible regulator of the long noncoding RNA H19.
作者信息
Safi Rémi, Mohsen-Kanson Tala, Nemer Georges, Dekmak Batoul, Rubeiz Nelly, El-Sabban Marwan, Nassar Dany, Eid Assaad, Abbas Ossama, Kibbi Abdul-Ghani, Kurban Mazen
机构信息
Department of Dermatology, American University of Beirut, Beirut, Lebanon.
Department of Biology, Faculty of Sciences, Lebanese University, Zahle, Lebanon.
出版信息
J Gastrointest Oncol. 2019 Oct;10(5):859-868. doi: 10.21037/jgo.2019.03.09.
BACKGROUND
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 was not depicted yet.
METHODS
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.
RESULTS
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 (HO) 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.
CONCLUSIONS
In conclusion, we showed that loss of FECH is protective against colon cancer tumorigenesis and this effect could possibly be mediated through inhibition of H19.
背景
亚铁螯合酶（FECH）是血红素生物合成途径中的最后一种酶。FECH缺乏与许多疾病相关，包括原卟啉症。相关性研究表明，在人类癌症中，尤其是在结肠癌中，检测到FECH表达的变化。然而，FECH在结肠癌致癌作用中的潜在作用尚未得到描述。
方法
使用小干扰RNA（siRNA）敲低人Caco-2结肠癌细胞中的FECH。在癌细胞中评估FECH下调对细胞增殖、迁移和靶基因表达的影响，并与人类正常成纤维细胞进行比较。
结果
FECH下调后，我们的结果表明Caco-2细胞的增殖未受影响。此外，仅当向培养基中施加额外的应激因子（HO）时，癌细胞和正常细胞的迁移才会受到影响。Caco-2细胞中twist、snail、缺氧诱导因子（HIF-1α）和血管内皮生长因子（VEGF）的表达降低。相反，在对照成纤维细胞中，VEGF和HIF-1α的表达上调了2倍。有趣的是，在FECH下调后，Caco-2细胞中致癌性长链非编码RNA（LncRNA）H19下调了70%，而在正常成纤维细胞中未观察到影响。
结论
总之，我们表明FECH的缺失对结肠癌的肿瘤发生具有保护作用，这种作用可能通过抑制H19来介导。
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