Qiupeng Zheng1,2, Jingjing Zhao1, Hui Yu2,3, Huajie Zong2, Xigan He2,4, Yiming Zhao2,4, Yan Li1,2, Yu Wang1, Yichao Bao1, Yuchen Li1,2, Bing Chen1,2, Weijie Guo1,2, Yilin Wang2,4, Zhiao Chen1,2, Yingjun Zhao1,2, Lu Wang2,4, Xianghuo He1,2, Shenglin Huang1,2. 1. Fudan University Shanghai Cancer Center, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. 3. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China. 4. Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Abstract
Hepatocellular carcinoma (HCC) is a highly lethal cancer and its underlying etiology remains understudied. The immense diversity and complexity of the cancer transcriptome hold the potential to yield tumor-specific transcripts (TSTs). Here, we showed that hundreds of TSTs are frequently expressed in HCC by an assembling spliced junction analysis of RNA sequencing raw data from approximately 1,000 normal and HCC tissues. Many of the TSTs were found to be unannotated and noncoding RNAs. We observed that intergenic TSTs are generated from transcription initiation sites frequently harboring long terminal repeat (LTR) elements. The strong presence of TSTs indicates significantly poor prognoses in HCC. Functional screening revealed a noncoding TST (termed TST1), which acted as a regulator of HCC cell proliferation and tumorigenesis. TST1 is generated from an LTR12C promoter regulated by DNA methylation and retinoic-acid-related drugs. Additionally, we observed that TSTs may be detected in the blood extracellular vesicles of patients with HCC. Conclusion: Our findings suggest an abundance of TSTs in HCC and their potential in clinical settings. The identification and characterization of TSTs may help toward the development of strategies for cancer diagnosis and treatment.
Hepatocellular carcinoma (HCC) is a highly lethal cancer and its underlying etiology remains understudied. The immense diversity and complexity of the cancer transcriptome hold the potential to yield tumor-specific transcripts (TSTs). Here, we showed that hundreds of TSTs are frequently expressed in HCC by an assembling spliced junction analysis of RNA sequencing raw data from approximately 1,000 normal and HCC tissues. Many of the TSTs were found to be unannotated and noncoding RNAs. We observed that intergenic TSTs are generated from transcription initiation sites frequently harboring long terminal repeat (LTR) elements. The strong presence of TSTs indicates significantly poor prognoses in HCC. Functional screening revealed a noncoding TST (termed TST1), which acted as a regulator of HCC cell proliferation and tumorigenesis. TST1 is generated from an LTR12C promoter regulated by DNA methylation and retinoic-acid-related drugs. Additionally, we observed that TSTs may be detected in the blood extracellular vesicles of patients with HCC. Conclusion: Our findings suggest an abundance of TSTs in HCC and their potential in clinical settings. The identification and characterization of TSTs may help toward the development of strategies for cancer diagnosis and treatment.