Wang Dan, Zhao Huijie, Zhao Ying, An Xuejing, Shi Chuanqin, Pan Zhaohai, Zheng Qiusheng, Wang Xin, Lu Jun, Li Defang
Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, PR China.
Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong, 264003, PR China.
Apoptosis. 2025 Apr;30(3-4):936-954. doi: 10.1007/s10495-024-02070-0. Epub 2025 Feb 4.
Growing research indicates that long noncoding RNAs (lncRNAs) are pivotal in the development and advancement of hepatocellular carcinoma (HCC). Our research pinpointed LINC01547 as a notable lncRNA that was significantly downregulated in Hep3B cells treated with bufotalin, whereas it exhibited elevated expression levels in HCC tumor tissues. Further study found that silencing LINC01547 markedly suppressed proliferation, induced apoptosis, and inhibited migration and invasion in Hep3B and HepG2 cells. LINC01547 knockdown reduced ADAR1 expression, which led to apoptosis and suppressed metastasis via inhibition of the FAK signaling pathway. Additionally, silencing LINC01547 upregulated miR-146b-5p, which in turn decreased RAC1 levels, further promoting apoptosis and inhibiting metastasis in HCC cells. In vivo, a Hep3B tumor-bearing mouse model confirmed the antitumor effects of LINC01547 silencing. Our findings demonstrate that LINC01547 regulates HCC cell apoptosis and metastasis through the ADAR1/FAK and miR-146b-5p/RAC1 pathways, suggesting that LINC01547 may serve as a biomarker and potential therapeutic target for HCC.
越来越多的研究表明，长链非编码RNA（lncRNA）在肝细胞癌（HCC）的发生和发展中起关键作用。我们的研究确定LINC01547是一种显著的lncRNA，在用蟾蜍灵处理的Hep3B细胞中它显著下调，而在HCC肿瘤组织中它表达水平升高。进一步研究发现，沉默LINC01547可显著抑制Hep3B和HepG2细胞的增殖、诱导凋亡，并抑制其迁移和侵袭。敲低LINC01547可降低ADAR1表达，通过抑制FAK信号通路导致细胞凋亡并抑制转移。此外，沉默LINC01547会上调miR-146b-5p，进而降低RAC1水平，进一步促进HCC细胞凋亡并抑制转移。在体内，Hep3B荷瘤小鼠模型证实了沉默LINC01547的抗肿瘤作用。我们的研究结果表明，LINC01547通过ADAR1/FAK和miR-146b-5p/RAC1途径调节HCC细胞凋亡和转移，提示LINC01547可能作为HCC的生物标志物和潜在治疗靶点。
