A LIN28B Tumor-Specific Transcript in Cancer

Publication date: 20 February 2018
Source:Cell Reports, Volume 22, Issue 8
Author(s): 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
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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Teaser

Guo et al. identified a tumor-specific LIN28B transcript variant, LIN28B-TST, in hepatocellular carcinoma and many other cancer types produced by alternative transcription initiation. The LIN28B-TST-expressing tumors may represent a subtype of aggressive cancer. LIN28B-TST could serve as an ideal and promising target candidate for cancer diagnosis and therapy.


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