title: IMP1 promotes choriocarcinoma cell migration and invasion through the novel effectors RSK2 and PPME1.
abstract: OBJECTIVE
  Oncofetal protein insulin-like growth factor II mRNA-binding protein 1 (IMP1) regulates cellular proliferation and migration. Expression of IMP1 is limited to a few adult human tissues. However, it commonly expresses in a variety of cancers. Our objective was to study the regulatory mechanism of IMP1 on the cellular functions of choriocarcinoma (CC) JAR cells.
  
  
  METHODS
  IMP1 protein levels were measured in CC tissues via immunohistochemistry. Specific siRNAs were used to down-regulate gene expressions. The abilities of migration and invasion were estimated by wound-healing and Matrigel chamber assays. The profile of IMP1-binding genes was investigated with an Agilent microarray. RT-qPCR, RNA immunoprecipitation, and IMP1 rescue experiments were performed to confirm the association between IMP1 and its binding genes. Gene expression was further analyzed by using RT-PCR and Western blotting.
  
  
  RESULTS
  Strong IMP1 expressions were frequently detected in CC tissues. Knockdown of IMP1 expression in JAR cells inhibited cell migration and invasion, but did not affect cellular proliferation and morphology. Microarray and RNA-immunoprecipitation results revealed several candidate genes regulated by IMP1. Among them, ribosomal protein S6 kinase (RSK2) and protein phosphatase methylesterase 1 (PPME1) were confirmed to be down-regulated in IMP1-depleted JAR cells. Re-expression of IMP1 into the cells restored the expressions of RSK2 and PPME1. Furthermore, the depletion of RSK2 or PPME1 decreased the migration and invasion of JAR cells.
  
  
  CONCLUSIONS
  Our results suggest that IMP1 plays an essential role in the regulation of migration and invasion of human CC cells, possibly through the novel effectors RSK2 and PPME1.
authors.affiliation: Department of Life Science, National Chung-Hsing University, 250 Kou-Kuang Rd, Taichung 40227, Taiwan; Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, 1650, Sec. 4, Taiwan Boulevard, Taichung 40705, Taiwan.
authors.forename: Yeun-Ting
authors.initials: YT
authors.lastname: Hsieh
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Chou
authors.forename: Hong-Chen
authors.initials: HC
authors.lastname: Chen
authors.forename: Jenn-Jhy
authors.initials: JJ
authors.lastname: Tseng
mesh_terms: D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002822:Choriocarcinoma / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C406144:IGF2BP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D019893:Ribosomal Protein S6 Kinases; D002265:Carboxylic Ester Hydrolases; C119357:protein phosphatase methylesterase-1
keywords: Choriocarcinoma; IMP1; Invasion; Migration