Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, People's Republic of China.
J Exp Clin Cancer Res. 2020 Apr 9;39(1):61. doi: 10.1186/s13046-020-01551-9.
Revealing the mechanical role of long non-coding RNAs (lncRNAs) in tumorigenesis can contribute to novel therapeutic target for cancers. The regulatory role of linc01134 in hepatocellular carcinoma (HCC) has not been studied yet.
qRT-PCR and western blot were conducted to measure relevant RNA and protein expressions. CCK-8, colony formation, EdU, flow cytometry, wound-healing, transwell assays and xenograft experiments were performed to determine the role of linc01134 in HCC. ChIP and luciferase reporter assays were performed to analyze the effects of Yin Yang-1 (YY1) on linc01134 transcription activity. Relevant mechanical experiments were performed to verify interaction between relative genes.
YY1 enhanced linc01134 transcription by interacting with linc01134 promoter. Knockdown of linc01134 inhibited proliferation, migration and epithelial-mesenchymal transition (EMT), yet promoting apoptosis in HCC cells. Mechanically, linc01134 acted as miR-324-5p sponge and interacted with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to increase the stability of YY1 mRNA expression. Up-regulated YY1 continuously stimulated linc01134 expression by enhancing linc01134 promoter activity, forming a positive feedback loop.
Linc01134/miR-324-5p/IGF2BP1/YY1 feedback loop mediates HCC progression, which possibly provide prognosis and treatment target of HCC.
揭示长链非编码 RNA(lncRNA)在肿瘤发生中的机械作用可以为癌症提供新的治疗靶点。lnc01134 在肝细胞癌(HCC)中的调节作用尚未得到研究。
qRT-PCR 和 Western blot 用于测量相关 RNA 和蛋白质的表达。CCK-8、集落形成、EdU、流式细胞术、划痕愈合、Transwell 测定和异种移植实验用于确定 linc01134 在 HCC 中的作用。ChIP 和荧光素酶报告基因测定用于分析 Yin Yang-1(YY1)对 linc01134 转录活性的影响。进行相关的机械实验以验证相对基因之间的相互作用。
YY1 通过与 linc01134 启动子相互作用增强 linc01134 转录。linc01134 的敲低抑制 HCC 细胞的增殖、迁移和上皮-间充质转化(EMT),但促进细胞凋亡。从机制上讲,linc01134 作为 miR-324-5p 的海绵体并与胰岛素样生长因子 2 mRNA 结合蛋白 1(IGF2BP1)相互作用,增加 YY1 mRNA 表达的稳定性。上调的 YY1 通过增强 linc01134 启动子活性不断刺激 linc01134 表达,形成正反馈环。
linc01134/miR-324-5p/IGF2BP1/YY1 反馈环介导 HCC 进展,这可能为 HCC 的预后和治疗提供靶标。