title: Genome-wide analysis of microRNA and mRNA expression signatures in hydroxycamptothecin-resistant gastric cancer cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center of Functional Genomics, Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Wu
authors.forename: Xiang-qiang
authors.initials: XQ
authors.lastname: Shao
authors.forename: Xian-xin
authors.initials: XX
authors.lastname: Meng
authors.forename: Xiao-na
authors.initials: XN
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Shi-xu
authors.initials: SX
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.forename: Hua-sheng
authors.initials: HS
authors.lastname: Xiao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D035683:MicroRNAs; D012333:RNA, Messenger; C028098:10-hydroxycamptothecin; D002166:Camptothecin