Department of Cell Biology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Anticancer Res. 2011 Jul;31(7):2453-9.
Oncogenic KRAS plays several key roles in a three-dimensional (3D) colonic-crypt model. However, miRNA expression regulated by oncogenic KRAS in this model is still elusive.
The differential expression of 105 cancer-related microRNAs was examined and compared in HCT116 cells and HKe3 cells (HCT116 cells in which mutated KRAS allele was deleted) in 3D culture. HKe3 cells stably overexpressing oncogenic KRAS and the public datasets for microRNA expression analysis of colorectal cancer were further examined.
The increased expression of miR-200c, miR-221 and miR-222 were observed exclusively in 3D culture, but not in the two-dimensional culture. These microRNAs were regulated by oncogenic KRAS and were significantly overexpressed in human colorectal tumor specimens. Of note, the protein expression level of Phosphatase and tensin homolog (PTEN), a putative target of miR-221/222 cluster, was reduced under the control of oncogenic KRAS in a 3D-specific manner.
Oncogenic KRAS regulates 3D-specific molecules, possibly being associated with colorectal tumor development in vivo.
致癌性 KRAS 在三维（3D）结肠隐窝模型中发挥着多种关键作用。然而，该模型中致癌性 KRAS 调节的 miRNA 表达仍不清楚。
在 3D 培养中，检测并比较了 HCT116 细胞和 HKe3 细胞（KRAS 突变等位基因缺失的 HCT116 细胞）中 105 种与癌症相关的 microRNA 的差异表达。进一步研究了稳定过表达致癌性 KRAS 的 HKe3 细胞和用于结直肠癌 microRNA 表达分析的公共数据集。
仅在 3D 培养中观察到 miR-200c、miR-221 和 miR-222 的表达增加，而在二维培养中则没有。这些 microRNAs 受致癌性 KRAS 调控，并在人类结直肠肿瘤标本中显著过表达。值得注意的是，PTEN（miR-221/222 簇的一个假定靶标）的蛋白表达水平在 3D 特异性条件下受到致癌性 KRAS 的控制而降低。
致癌性 KRAS 调节 3D 特异性分子，可能与体内结直肠肿瘤的发展有关。
