International Medical Center, The General Hospital of Chinese People's Liberation Army, Beijing, 100853, China.
Lung Cancer. 2012 Sep;77(3):488-94. doi: 10.1016/j.lungcan.2012.05.107. Epub 2012 Jun 30.
Cisplatin is a classic chemotherapy agent used for treating human non-small cell lung cancer (NSCLC). However, cisplatin resistance is a challenge against successful clinical use. Glutathione S-transferase P1 (GSTP1) has been reported to contribute to cisplatin resistance in many studies. MicroRNAs (miRNAs) are short non-coding RNAs that are 21-25 nucleotides in length. They play a role in post-transcriptional gene regulation by inducing repression and/or mRNA degradation. Recent studies have shown that miRNAs are responsible for cisplatin resistance. This study aims to determine whether deregulated miRNAs can sensitize human lung adenocarcinoma cells to cisplatin by targeting GSTP1. Real-time RT-PCR revealed that GSTP1 mRNA expression was 2.7 ± 0.38 folds (p=0.039) upregulated in A549/CDDP cells, compared with the parental A549 cells, while miR-513a-3p expression was 0.34 ± 0.03 folds (p=0.023) downregulated. Luciferase activity assay proved that GSTP1 was a target gene of miR-513a-3p, which was confirmed by Western blot analysis. Furthermore, CCK-8 assay showed that overexpression of miR-513a-3p could enhance cisplatin-induced apoptosis in human lung adenocarcinoma cell lines, A549/CDDP and SPC-A-1. In conclusion, our data demonstrated that miR-513a-3p can sensitize human lung adenocarcinoma cells to cisplatin by targeting GSTP1.
顺铂是一种经典的化疗药物,用于治疗人类非小细胞肺癌(NSCLC)。然而,顺铂耐药性是成功临床应用的挑战。谷胱甘肽 S-转移酶 P1(GSTP1)在许多研究中被报道有助于顺铂耐药性。microRNAs(miRNAs)是长度为 21-25 个核苷酸的短非编码 RNA。它们通过诱导抑制和/或 mRNA 降解在转录后基因调控中发挥作用。最近的研究表明,miRNAs 负责顺铂耐药性。本研究旨在通过靶向 GSTP1 确定失调的 miRNAs 是否可以使人类肺腺癌细胞对顺铂敏感。实时 RT-PCR 显示,与亲本 A549 细胞相比,A549/CDDP 细胞中 GSTP1 mRNA 表达上调 2.7 ± 0.38 倍(p=0.039),而 miR-513a-3p 表达下调 0.34 ± 0.03 倍(p=0.023)。荧光素酶活性测定证实 GSTP1 是 miR-513a-3p 的靶基因,Western blot 分析证实了这一点。此外,CCK-8 测定表明,miR-513a-3p 的过表达可以增强人类肺腺癌细胞系 A549/CDDP 和 SPC-A-1 中顺铂诱导的细胞凋亡。总之,我们的数据表明,miR-513a-3p 通过靶向 GSTP1 可以使人类肺腺癌细胞对顺铂敏感。