A LIN28B Tumor-Specific Transcript in Cancer

Weijie Guo; Zhixiang Hu; Yichao Bao; Yuchen Li; Shengli Li; Qiupeng Zheng; Dongbin Lyu; Di Chen; Tao Yu; Yan Li; Xiaodong Zhu; Jie Ding; Yingjun Zhao; Xianghuo He; Shenglin Huang

doi:10.1016/j.celrep.2018.02.002

A LIN28B Tumor-Specific Transcript in Cancer

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

Authors

Weijie Guo¹, Zhixiang Hu², Yichao Bao³, Yuchen Li³, Shengli Li³, Qiupeng Zheng³, Dongbin Lyu³, Di Chen³, Tao Yu⁴, Yan Li³, Xiaodong Zhu³, Jie Ding³, Yingjun Zhao³, Xianghuo He⁵, Shenglin Huang⁶

Affiliations

¹ Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Markey Cancer Center, College of Medicine, University of Kentucky, Lexington, KY 40506, USA.
² Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
³ Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
⁴ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
⁵ Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
⁶ Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: [email protected].

PMID: 29466730
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