LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells
LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells
复制标题
DOI：
10.1016/j.lfs.2018.02.006
复制
发表时间：
2018-03-15
期刊：
影响因子：
6.1
通讯作者：
Guo, Zhi
中科院分区：
文献类型：
--
作者：
Li, Baoguo;Mao, Rui;Guo, Zhi
背景：长链非编码rna （LncRNAs）已被证明在肝细胞癌（HCC）的肿瘤生长和转移中起着至关重要的作用。LncRNA FAL1已被证实可促进多种癌症的进展。然而，lncRNA FAL1在HCC中的作用尚不清楚。方法：采用RT-qPCR法检测lncRNA FAL1在HCC组织和细胞中的表达水平。采用MTT、集落形成、transwell、RT-qPCR、Western blotting等方法研究lncRNA FAL1在HCC细胞中的作用。使用RegRNA 2.0预测lncRNA FAL1的miRNA结合位点，并通过荧光素酶报告基因检测和RT-qPCR验证miR-1236靶向lncRNA FAL1。最后，我们还研究了lncRNA FAL1在HCC患者血清外泌体中的表达水平，并通过与HCC细胞共培养进一步研究了外泌体介导的lncRNA FAL1的作用。结果：本研究首次发现lncRNA FAL1在HCC组织中表达上调，并在HCC中发挥致癌基因的作用。LncRNA FAL1通过与miR-1236的竞争性结合，作为ceRNA机制加速细胞增殖和转移。此外，lncRNA FAL1在HCC患者的血清外泌体中也表达上调，并可将lncRNA FAL1转移到HCC细胞中，提高HCC细胞的增殖和迁移能力。结论：综上所述，本研究提示lncRNA FAL1在HCC中具有致癌作用，未来可能成为HCC新的诊断生物标志物或新的治疗靶点。
Background: Long non-coding RNAs (LncRNAs) have been demonstrated to play crucial role in tumor growth and metastasis for hepatocellular carcinoma (HCC). LncRNA FAL1 has been indicated to promote the progression of various cancers. However, the role of lncRNA FAL1 in HCC was poorly understood.Methods: The expression levels of lncRNA FAL1 in HCC tissues and cells were determined by RT-qPCR. The roles of lncRNA FAL1 on HCC cells were investigated by MTT, colony formation, transwell, RT-qPCR, and Western blotting. The miRNA binding sites of lncRNA FAL1 was predicted using RegRNA 2.0 and miR-1236 was validated to target lncRNA FAL1 by luciferase reporter assays and RT-qPCR. Finally, the expression levels of lncRNA FAL1 in serum exosome of HCC patients was also investigated and the role of exosome-mediated lncRNA FAL1 was further investigated by co-culturing with HCC cells.Results: This study first showed that lncRNA FAL1 was up-regulated in HCC tissues and functioned as an oncogene in HCC. LncRNA FAL1 could accelerate cell proliferation and metastasis as a ceRNA mechanism by competitively binding to miR-1236. Moreover, lncRNA FAL1 was also up-regulated in serum exosome of HCC patients and could transfer lncRNA FAL1 to HCC cells to increase their abilities of cell proliferation and migration.Conclusions: Taken together, this study indicated that lncRNA FAL1 functions as an oncogenic in HCC and may be a novel diagnostic biomarker or a novel target for the treatment of HCC in future.