Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Several studies have identified signature gene sets that may be useful as potential diagnostic tools by global microarray analysis. Here we report the cloning and characterization of a novel gene, lin-28 homolog B (LIN28B), which is overexpressed in hepatocellular carcinoma. The heterochronic gene lin-28 is a key regulator of developmental timing in the nematode Caenorhabditis elegans. Similar with lin-28 proteins, LIN28B conserves a cold shock domain and a pair of CCHC zinc finger domains. Phylogenetic analysis suggests that they might arise as a result of duplication from an ancestral gene. Overexpression of LIN28B was noted in most HCC cell lines and clinical samples. By western blot analysis using a polyclonal antibody against LIN28B, a short LIN28B isoform was also identified in non-tumor liver tissue and fetal liver. Although predominantly localized in the cytoplasm, we found that LIN28B protein shows cell cycle-dependent nuclear translocation in Huh7 cells. Induced expression of exogenous LIN28B in a tet-off cell line promoted cancer cell proliferation. Interestingly, the segment of the unusually long 3'UTR of LIN28B contains complementary sites to let-7 microRNA of mammals. And our studies provided indirect evidence that LIN28B is a possibly natural target for let-7 mediated regulation. These findings strongly implicate a critical role of LIN28B during development and tumorigenesis and suggest a possible novel mechanism.
Guo
Yingqiu
Y
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
Chen
Yongxin
Y
Ito
Hirotaka
H
Watanabe
Akira
A
Ge
Xijin
X
Kodama
Tatsuhiko
T
Aburatani
Hiroyuki
H
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D029742:Caenorhabditis elegans Proteins; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D008969:Molecular Sequence Data; D021141:Nucleic Acid Amplification Techniques; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016335:Zinc Fingers
D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C410586:LIN-41 protein, C elegans; C516326:LIN28B protein, human; D035683:MicroRNAs; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D014157:Transcription Factors