Department of Pathology, School of Medicine, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea.
Digestive Disease Research Institute, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea.
Pathol Oncol Res. 2019 Jul;25(3):953-959. doi: 10.1007/s12253-018-0399-3. Epub 2018 Mar 12.
MiRNAs are non-coding RNAs that play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. Previously we identified colorectal cancer (CRC) associated MIR196B, which was specifically up-regulated in CRC cells and tissue. We also identified 18 putative MIR196B target genes by comparing the mRNAs down-regulated in MIR196B-overexpressed cells with MIR196B target genes predicted by public bioinformatics tools. In this study, we verified the association between MIR196B and three genes, HOXA5, HOXB6 and GLTP. HOXA5, HOXB6 and GLTP transcripts were directly down-regulated by MIR196B. The mRNA and proteins levels of HOXA5, HOXB6 and GLTP were also down-regulated in CRC cells by the up-regulated MIR196B. GLTP protein expression was decreased in CRC tissues compared to adjacent non-tumor tissues. These results suggest that HOXA5, HOXB6, and GLTP were direct target genes of MIR196B in CRC cells, and that the up-regulated MIR196B in CRC tissue regulates the expression levels of HOXA5, HOXB6, and GLTP during colorectal carcinogenesis.
miRNAs 是一类非编码 RNA，通过在特定细胞或组织中调节靶基因的表达，在人类疾病的发病机制中发挥重要作用。之前我们鉴定了与结直肠癌（CRC）相关的 MIR196B，其在 CRC 细胞和组织中特异性地上调。我们还通过比较 MIR196B 过表达细胞中下调的 mRNAs 与公共生物信息学工具预测的 MIR196B 靶基因，鉴定了 18 个假定的 MIR196B 靶基因。在这项研究中，我们验证了 MIR196B 与三个基因 HOXA5、HOXB6 和 GLTP 之间的关联。HOXA5、HOXB6 和 GLTP 的转录本直接受到 MIR196B 的下调。MIR196B 上调也下调了 CRC 细胞中 HOXA5、HOXB6 和 GLTP 的 mRNA 和蛋白水平。CRC 组织中 GLTP 蛋白表达较癌旁非肿瘤组织降低。这些结果表明，HOXA5、HOXB6 和 GLTP 是 CRC 细胞中 MIR196B 的直接靶基因，CRC 组织中上调的 MIR196B 在结直肠癌变过程中调节 HOXA5、HOXB6 和 GLTP 的表达水平。
