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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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.
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.
Guo, Weijie; Hu, Zhixiang; Bao, Yichao; Li, Yuchen; Li, Shengli; Zheng, Qiupeng; Lyu, Dongbin; Chen, Di; Yu, Tao; Li, Yan; Zhu, Xiaodong; Ding, Jie; Zhao, Yingjun; He, Xianghuo; and Huang, Shenglin, "A LIN28B Tumor-Specific Transcript in Cancer" (2018). Markey Cancer Center Faculty Publications. 105.
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