Zhang Shuai, Duan Juanjuan, Du Yu, Xie Jinlu, Zhang Haijing, Li Changyu, Zhang Wensheng
International Cooperation Laboratory of Molecular Medicine, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Zhuhai Branch of State Key Laboratory of Earth Surface Processes and Resource Ecology, Advanced Institute of Natural Sciences, Beijing Normal University at Zhuhai, Zhuhai, China.
Front Cell Dev Biol. 2021 Jul 22;9:698442. doi: 10.3389/fcell.2021.698442. eCollection 2021.
The liver is sensitive to aging because the risk of hepatopathy, including fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, increases dramatically with age. Long non-coding RNAs (lncRNAs) are >200 nucleotides long and affect many pathological and physiological processes. A potential link was recently discovered between lncRNAs and liver aging; however, comprehensive and systematic research on this topic is still limited. In this study, the mouse liver genome-wide lncRNA profiles of 8-month-old SAMP8 and SAMR1 models were explored through deep RNA sequencing. A total of 605,801,688 clean reads were generated. Among the 2,182 identified lncRNAs, 28 were differentially expressed between SAMP8 and SAMR1 mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) surveys showed that these substantially dysregulated lncRNAs participated in liver aging from different aspects, such as lipid catabolic (GO: 0016042) and metabolic pathways. Further assessment was conducted on lncRNAs that are most likely to be involved in liver aging and related diseases, such as LNC_000027, LNC_000204E, NSMUST00000144661.1, and ENSMUST00000181906.1 acted on Ces1g. This study provided the first comprehensive dissection of lncRNA landscape in SAMP8 mouse liver. These lncRNAs could be exploited as potential targets for the molecular-based diagnosis and therapy of age-related liver diseases.
肝脏对衰老敏感，因为包括脂肪肝、肝炎、纤维化、肝硬化和肝细胞癌在内的肝病风险会随着年龄的增长而急剧增加。长链非编码RNA（lncRNA）长度超过200个核苷酸，并影响许多病理和生理过程。最近发现lncRNA与肝脏衰老之间存在潜在联系；然而，关于这一主题的全面系统研究仍然有限。在本研究中，通过深度RNA测序探索了8月龄SAMP8和SAMR1模型小鼠肝脏全基因组lncRNA图谱。共产生了605,801,688条干净 reads。在鉴定出的2182个lncRNA中，有28个在SAMP8和SAMR1小鼠之间差异表达。基因本体论（GO）和京都基因与基因组百科全书（KEGG）研究表明，这些显著失调的lncRNA从不同方面参与肝脏衰老，如脂质分解代谢（GO:0016042）和代谢途径。对最有可能参与肝脏衰老及相关疾病的lncRNA进行了进一步评估，如LNC_000027、LNC_000204E、NSMUST00000144661.1和ENSMUST00000181906.1作用于Ces1g。本研究首次全面剖析了SAMP8小鼠肝脏中的lncRNA景观。这些lncRNA可作为基于分子的年龄相关性肝病诊断和治疗的潜在靶点。
