title: The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function.
abstract: The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13.3 that is frequency deleted in MDL patients and in human liver cancer cells. However, the expression and significance of LIS1 in liver cancer remain unknown. Here, we investigated the expression of LIS1 in hepatocellular carcinoma (HCC) tissues by real-time PCR, Western blot, and immunohistochemistry. The results indicated that the mRNA and protein levels of LIS1 were downregulated in about 70% of HCC tissues, and this downregulation was significantly associated with tumor progression. Functional studies showed that the reduction of LIS1 expression in the normal human liver cell line QSG7701 or the mouse fibroblast cell line NIH3T3 by shRNA resulted in colony formation in soft agar and xenograft tumor formation in nude mice, demonstrating that a decrease in the LIS1 level can promote the oncogenic transformation of cells. We also observed that the phenotypes of LIS1-knockdown cells displayed various defective mitotic structures, suggesting that the mechanism by which reduced LIS1 levels results in tumorigenesis is associated with its role in mitosis. Furthermore, we demonstrated that ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. Our results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of HCC.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xing
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Liang
authors.initials: L
authors.lastname: Da
authors.forename: Hai
authors.initials: H
authors.lastname: Song
authors.forename: Suiquan
authors.initials: S
authors.lastname: Wang
authors.forename: Pierre
authors.initials: P
authors.lastname: Tiollais
authors.forename: Tsaiping
authors.initials: T
authors.lastname: Li
authors.forename: Mujun
authors.initials: M
authors.lastname: Zhao
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D041702:BALB 3T3 Cells; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human