title: Snail as a key regulator of PRL-3 gene in colorectal cancer.
abstract: The regulators of a key metastasis gene PRL-3 in colorectal cancer (CRC) are still largely unknown. We found three potential binding sites of Snail, a key transcriptional factor involved in the epithelial-mesenchymal transition (EMT), in the region of PRL-3 promoter (located at -642 to -383). Moreover, our results showed that one of the Snail binding sites (located at -624 to -619) was the key element to maintain promoter activity of human PRL-3 gene. The transcriptional activity of PRL-3 promoter was abolished after the Snail binding site (located at -624 to -619) was mutated. Both promoter activity and protein expression of PRL-3 in CRC cell lines could be regulated by Snail. In clinical samples of CRC and metastatic lymph node of CRC, expression of PRL-3 protein was correlated with expression of Snail protein. Functional studies using gene over-expression and knockdown methods indicated that Snail promoted proliferation, cell adhesion and migration of human CRC cells. In SW480 cells with PRL-3 stable knockdown, cell proliferation increased after Snail was up-regulated. Our data first reveal transcriptional factor Snail as a key regulator of PRL-3 in CRC. The link between Snail and PRL-3 suggests a new potential mechanism of Snail contributing to progression and metastasis of CRC.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Meng
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Gao
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Xun-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Zheng-Quan
authors.initials: ZQ
authors.lastname: Xiao
authors.forename: Yong-Xia
authors.initials: YX
authors.lastname: Liu
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Sui
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Liu
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D002448:Cell Adhesion / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D009363:Neoplasm Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases