A LIN28B Tumor-Specific Transcript in Cancer

Cell Rep. 2018 Feb 20;22(8):2016-2025. doi: 10.1016/j.celrep.2018.02.002.

Abstract

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer cell proliferation and tumorigenesis. Our findings reveal a mechanism of LIN28B activation in cancer and the potential utility of LIN28B-TST for clinical purposes.

Keywords: LIN28B; oncogene; tumor-specific transcript.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Demethylation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / genetics*
  • Promoter Regions, Genetic
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Sequence Analysis, RNA
  • Transcription, Genetic

Substances

  • LIN28B protein, human
  • Protein Isoforms
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA-Binding Proteins