MEK抑制剂抑制HT-29人结肠癌细胞和MIA PaCa-2胰腺癌细胞中miR-17-92簇的表达并导致G1期阻滞。
MEK Inhibitor Suppresses Expression of the miR-17-92 Cluster with G1-Phase Arrest in HT-29 Human Colon Cancer Cells and MIA PaCa-2 Pancreatic Cancer Cells.
作者信息
Tanaka Ryoichi, Tomosugi Mitsuhiro, Sakai Toshiyuki, Sowa Yoshihiro
机构信息
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan.
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan
出版信息
Anticancer Res. 2016 Sep;36(9):4537-43. doi: 10.21873/anticanres.11001.
BACKGROUND
MicroRNAs (miRNAs) are small non-coding RNAs, and the deregulated expression of miRNAs is associated with tumor development. Among these, the miR-17-92 cluster, including six mature miRNAs, is known as an oncogenic miRNA cluster because expression of the miR-17-92 cluster is frequently elevated in a variety of malignant tumors.
MATERIALS AND METHODS
We investigated whether a mitogen-activated protein kinase kinase (MEK) inhibitor, PD0325901, suppresses expression of the miR-17-92 cluster in HT-29 human colon cancer cells and MIA PaCa-2 pancreatic cancer cells.
RESULTS
PD0325901 inhibited cell growth with G1-phase arrest and suppressed expression of the miR-17-92 cluster. Furthermore, phosphatase and tensin homolog (PTEN), which is a target molecule of the miR-17-92 cluster, was up-regulated by PD0325901. The exogenous expression of miR-17 slightly, but significantly reduced G1-phase arrest by PD0325901.
CONCLUSION
These results raise the possibility that a MEK inhibitor causes G1-phase arrest, at least partially, through suppression of the miR-17-92 cluster.
背景
微小RNA（miRNA）是一类小的非编码RNA，其表达失调与肿瘤发生发展相关。其中，包含6个成熟miRNA的miR-17-92簇被认为是一个致癌性miRNA簇，因为在多种恶性肿瘤中miR-17-92簇的表达常常升高。
材料与方法
我们研究了丝裂原活化蛋白激酶激酶（MEK）抑制剂PD0325901是否能抑制HT-29人结肠癌细胞和MIA PaCa-2胰腺癌细胞中miR-17-92簇的表达。
结果
PD0325901通过使细胞周期停滞于G1期抑制细胞生长，并抑制miR-17-92簇的表达。此外，miR-17-92簇的靶分子磷酸酶和张力蛋白同源物（PTEN）被PD0325901上调。miR-17的外源性表达略微但显著地减少了PD0325901引起的G1期停滞。
结论
这些结果提示，MEK抑制剂至少部分地通过抑制miR-17-92簇导致G1期停滞。
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