Genome-wide analysis of microRNA and mRNA expression signatures in hydroxycamptothecinresistant gastric cancer cells  

作　　者：Xue-mei WU Xiang-qiang SHAO Xian-xin MENG Xiao-na ZHANG LiZHU Shi-xu LIU Jian LIN Hua-sheng XIAO 

机构地区：[1]The Center of Functional Genomics, Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2]National Engineering Center for Biochip at Shanghai, Shanghai 201203, China [3]Graduate University of Chinese Academy of Sciences, Shanghai 200031, China

出　　处：《Acta Pharmacologica Sinica》2011年第2期259-269,共11页中国药理学报（英文版）

摘　　要：Aim： 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）. Methods： 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. Results： 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. Conclusion： 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.Aim： 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）. Methods： 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. Results： 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. Conclusion： 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.

关 键 词：hydroxycamptothecin （HCPT） gastric cancer MICRORNA signature drug resistance gene expression regulation cluster analysis messenger RNA 

分 类 号：R[医药卫生]