Identification and Characterization of lin-28 Homolog B (LIN28B) in Human Hepatocellular Carcinoma

Gene. 2006 Dec 15;384:51-61. doi: 10.1016/j.gene.2006.07.011. Epub 2006 Jul 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans Proteins
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Cytoplasm / metabolism
  • DNA, Complementary
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Liver / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Mice
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Nucleic Acid Amplification Techniques
  • Oligonucleotide Array Sequence Analysis
  • Phylogeny
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA-Binding Proteins
  • Transcription Factors
  • Zinc Fingers

Substances

  • 3' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • LIN-41 protein, C elegans
  • LIN28B protein, human
  • MicroRNAs
  • Protein Isoforms
  • RNA-Binding Proteins
  • Transcription Factors