Laboratorio de Terapia Génica, Departamento de Genética y Biología Molecular, CINVESTAV, Av. IPN 2508, México 07360 DF, Mexico.
Biochem Biophys Res Commun. 2011 Jun 10;409(3):513-9. doi: 10.1016/j.bbrc.2011.05.036. Epub 2011 May 11.
MicroRNAs (miRNA) regulate expression of several genes associated with human cancer. Here, we analyzed the function of miR-34c, an effector of p53, in cervical carcinoma cells. Expression of either miR-34c-3p or miR-34c-5p mimics caused inhibition of cell proliferation in the HPV-containing SiHa cells but not in other cervical cells irrespective of tumorigenicity and HPV content. These results suggest that SiHa cells may lack of regulatory mechanisms for miR-34c. Monolayer proliferation results showed that miR-34c-3p produced a more pronounced inhibitory effect although both miRNAs caused inhibition of anchorage independent growth at similar extent. However, ectopic expression of pre-miR-34c-3p, but not pre-miR-34c-5p, caused S-phase arrest in SiHa cells triggering a strong dose-dependent apoptosis. A significant inhibition was observed only for miR-34c-3p on SiHa cells migration and invasion, therefore implying alternative regulatory pathways and targets. These results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights in the understanding of miRNA biology.
MicroRNAs (miRNA) 调节与人类癌症相关的几个基因的表达。在这里，我们分析了 p53 效应物 miR-34c 在宫颈癌细胞中的功能。miR-34c-3p 或 miR-34c-5p 模拟物的表达导致 HPV 含有的 SiHa 细胞而非其他宫颈细胞的增殖受到抑制，而与致瘤性和 HPV 含量无关。这些结果表明 SiHa 细胞可能缺乏 miR-34c 的调节机制。单层增殖结果表明 miR-34c-3p 产生更明显的抑制作用，尽管两种 miRNA 以相似的程度抑制了锚定非依赖性生长。然而，外源性表达 pre-miR-34c-3p，但不是 pre-miR-34c-5p，导致 SiHa 细胞 S 期停滞，引发强烈的剂量依赖性凋亡。仅 miR-34c-3p 对 SiHa 细胞的迁移和侵袭有明显抑制作用，因此暗示存在替代的调节途径和靶标。这些结果表明 miR-34c-3p 和 miR-34c-5p 具有不同的肿瘤抑制作用，并为 miRNA 生物学的理解提供了新的见解。
