Jiang Hao, Shi Xuefei, Ye Guochao, Xu Yongcan, Xu Jiewei, Lu Jun, Lu Wei
Department of General Surgery, Huzhou Central Hospital, Huzhou, People's Republic of China.
Department of Respiratory Medicine, Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, People's Republic of China.
Onco Targets Ther. 2019 Sep 11;12:7429-7436. doi: 10.2147/OTT.S214336. eCollection 2019.
Long non-coding RNAs (lncRNAs) are implicated as novel factors in tumorigenesis and tumor progression. Although thousands of lncRNAs have been discovered, only a small portion have been functionally determined in hepatocellular carcinoma (HCC). Here, we aimed to comprehensively analyze differentially expressed lncRNAs, evaluate their clinical significance, and explore the functional roles and underlying mechanism in HCC.
We identified hundreds of lncRNAs which were dysregulated in HCC tissues through performing integrative analyses using the RNA sequencing data and independent gene microarray data from Gene Expression Omnibus and the Cancer Genome Atlas.
Dysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients' poor outcomes. Further experimental validation revealed that down-regulation of lncRNA DUXAP8 inhibited HCC cells proliferation and colony formation ability. Mechanistically, DUXAP8 repressed tumor suppressor KLF2 transcription through interacting with histone-lysine N-methyltransferase enzyme enhancer of zeste homolog 2.
Taken together, our findings can provide a valuable resource of HCC-associated lncRNAs and new insights into the biological functions of lncRNAs in HCC development.
长链非编码RNA（lncRNAs）被认为是肿瘤发生和进展中的新因素。尽管已发现数千种lncRNAs，但在肝细胞癌（HCC）中只有一小部分的功能已被确定。在此，我们旨在全面分析差异表达的lncRNAs，评估其临床意义，并探索其在HCC中的功能作用及潜在机制。
我们通过对来自基因表达综合数据库（Gene Expression Omnibus）和癌症基因组图谱（Cancer Genome Atlas）的RNA测序数据及独立基因芯片数据进行综合分析，鉴定出数百种在HCC组织中失调的lncRNAs。
失调的DUXAP8、LINC01116、LINC01138和PCAT6与HCC患者的不良预后显著相关。进一步的实验验证表明，lncRNA DUXAP8的下调抑制了HCC细胞的增殖和集落形成能力。机制上，DUXAP8通过与组蛋白赖氨酸N-甲基转移酶zeste同源物2的增强子相互作用抑制肿瘤抑制因子KLF2的转录。
综上所述，我们的研究结果可为HCC相关lncRNAs提供有价值的资源，并为lncRNAs在HCC发生发展中的生物学功能提供新的见解。
