Selitsky Sara R, Baran-Gale Jeanette, Honda Masao, Yamane Daisuke, Masaki Takahiro, Fannin Emily E, Guerra Bernadette, Shirasaki Takayoshi, Shimakami Tetsuro, Kaneko Shuichi, Lanford Robert E, Lemon Stanley M, Sethupathy Praveen
1] Bioinformatics and Computational Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [2] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [3] Departments of Medicine and Microbiology &Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [4] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
1] Bioinformatics and Computational Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America [2] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Sci Rep. 2015 Jan 8;5:7675. doi: 10.1038/srep07675.
Persistent infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) account for the majority of cases of hepatic cirrhosis and hepatocellular carcinoma (HCC) worldwide. Small, non-coding RNAs play important roles in virus-host interactions. We used high throughput sequencing to conduct an unbiased profiling of small (14-40 nts) RNAs in liver from Japanese subjects with advanced hepatitis B or C and hepatocellular carcinoma (HCC). Small RNAs derived from tRNAs, specifically 30-35 nucleotide-long 5' tRNA-halves (5' tRHs), were abundant in non-malignant liver and significantly increased in humans and chimpanzees with chronic viral hepatitis. 5' tRH abundance exceeded microRNA abundance in most infected non-cancerous tissues. In contrast, in matched cancer tissue, 5' tRH abundance was reduced, and relative abundance of individual 5' tRHs was altered. In hepatitis B-associated HCC, 5' tRH abundance correlated with expression of the tRNA-cleaving ribonuclease, angiogenin. These results demonstrate that tRHs are the most abundant small RNAs in chronically infected liver and that their abundance is altered in liver cancer.
全球范围内，乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）的持续感染是肝硬化和肝细胞癌（HCC）的主要病因。小型非编码RNA在病毒与宿主的相互作用中发挥着重要作用。我们利用高通量测序技术，对患有晚期乙型或丙型肝炎及肝细胞癌（HCC）的日本受试者肝脏中的小型（14 - 40个核苷酸）RNA进行了无偏差分析。源自转运RNA（tRNA）的小型RNA，特别是长度为30 - 35个核苷酸的5' tRNA半体（5' tRHs），在非恶性肝脏中含量丰富，并且在患有慢性病毒性肝炎的人类和黑猩猩体内显著增加。在大多数受感染的非癌组织中，5' tRH的丰度超过了微小RNA的丰度。相反，在匹配的癌组织中，5' tRH的丰度降低，且单个5' tRH的相对丰度发生了改变。在乙型肝炎相关的肝细胞癌中，5' tRH的丰度与切割tRNA的核糖核酸酶血管生成素的表达相关。这些结果表明，tRHs是慢性感染肝脏中最丰富的小型RNA，并且它们在肝癌中的丰度发生了改变。
