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.

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Notes/Citation Information

Published in Cell Reports, v. 22, issue 8, p. 2016-2025.

© 2018 The Author(s).

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Funding Information

Our work is supported by grants from the National Natural Science Foundation of China (81472617 and 81672779) and Key Laboratory of Gene Engineering of the Ministry of Education.

Related Content

The accession numbers for raw sequencing data reported in this study are GEO: GSE77661 (tissue RNA-seq), GEO: GSE109528 (cell RNA-seq), and GEO: GSE109575 (ChIP-seq).

Supplemental Information includes Supplemental Experimental Procedures, four figures, and three tables and can be found with this article online at https://doi.org/10.1016/j.celrep.2018.02.002.

mmc1.pdf (2674 kB)
Document S1. Supplemental Experimental Procedures, Figures S1–S4, and Table S2

mmc2.xlsx (330 kB)
Table S1. The List of Potential Tumor-Specific Transcripts Identified by RNA-Seq Analyses, Related to Figure 1

mmc3.xlsx (13 kB)
Table S3. Primers and Oligo Sequences Used in This Study, Related to Experimental Procedures