A LIN28B Tumor-Specific Transcript in Cancer

• Published in: Cell reports (Cambridge) Vol. 22; no. 8; pp. 2016 - 2025
• Main Authors: 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, Huang, Shenglin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.02.2018; Elsevier
• Subjects: LIN28B; oncogene; tumor-specific transcript; oncogene; tumor-specific transcript; LIN28B
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.02.002

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. [Display omitted] •RNA-seq analyses reveal a LIN28B tumor-specific variant in cancers•LIN28B-TST initiates from an ATI site regulated by NFYA but not c-Myc•LIN28B-TST expression is controlled by DNA methylation•LIN28B-TST is critical for cancer cell proliferation and tumorigenesis 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.