Center of Functional Genomics, Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Acta Pharmacol Sin. 2011 Feb;32(2):259-69. doi: 10.1038/aps.2010.204.
To investigate the involvement of microRNAs (miRNAs) in intrinsic drug resistance to hydroxycamptothecin (HCPT) of six gastric cancer cell lines (BGC-823, SGC-7901, MGC-803, HGC-27, NCI-N87, and AGS).
A sulforhodamine B (SRB) assay was used to analyze the sensitivity to HCPT of six gastric cancer cell lines. The miRNA and mRNA expression signatures in HCPT-resistant cell lines were then identified using DNA microarrays. Gene ontology and pathway analysis was conducted using GenMAPP2. A combined analysis was used to explore the relationship between the miRNAs and mRNAs.
The sensitivity to HCPT was significantly different among the six cell lines. In the HCPT-resistant gastric cancer cells, the levels of 25 miRNAs were deregulated, including miR-196a, miR-200 family, miR-338, miR-126, miR-31, miR-98, let-7g, and miR-7. Their target genes were related to cancer development, progression and chemosensitivity. Moreover, 307 genes were differentially expressed in HCPT-resistant cell lines, including apoptosis-related genes (BAX, TIAL1), cell division-related genes (MCM2), cell adhesion- or migration-related genes (TIMP2, VSNL1) and checkpoint genes (RAD1). The combined analysis revealed 78 relation pairs between the miRNAs and mRNAs.
Hierarchical clustering showed that the miRNA and mRNA signatures in our results were informative for discriminating cell lines with different sensitivities to HCPT. However, there was slightly lower correlation between the expression patterns of the miRNA and those of the predicted target transcripts.
研究 microRNAs（miRNAs）在 6 株胃癌细胞系（BGC-823、SGC-7901、MGC-803、HGC-27、NCI-N87 和 AGS）内在性对羟基喜树碱（HCPT）耐药中的作用。
采用磺酰罗丹明 B（SRB）法分析 6 株胃癌细胞系对 HCPT 的敏感性。然后，利用 DNA 微阵列鉴定 HCPT 耐药细胞系中的 miRNA 和 mRNA 表达谱。利用 GenMAPP2 进行基因本体论和通路分析。采用联合分析方法探索 miRNA 和 mRNA 之间的关系。
6 株细胞系对 HCPT 的敏感性差异有统计学意义。在 HCPT 耐药的胃癌细胞中，25 个 miRNA 的水平失调，包括 miR-196a、miR-200 家族、miR-338、miR-126、miR-31、miR-98、let-7g 和 miR-7。它们的靶基因与癌症的发生、发展和化疗敏感性有关。此外，在 HCPT 耐药细胞系中，有 307 个基因差异表达，包括凋亡相关基因（BAX、TIAL1）、细胞分裂相关基因（MCM2）、细胞黏附或迁移相关基因（TIMP2、VSNL1）和检查点基因（RAD1）。联合分析显示 miRNA 和 mRNA 之间存在 78 对关系。
层次聚类显示，miRNA 和 mRNA 特征在区分对 HCPT 敏感性不同的细胞系方面具有信息性。然而，miRNA 表达模式与预测靶转录物之间的相关性略低。
