长链非编码 RNA FAL1 通过作为肝细胞癌细胞中 miR-1236 的 ceRNA 促进细胞增殖和迁移。
LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells.
机构信息
Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, Chinese National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, Chinese National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
出版信息
Life Sci. 2018 Mar 15;197:122-129. doi: 10.1016/j.lfs.2018.02.006. Epub 2018 Feb 6.
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.
背景
长链非编码 RNA（lncRNA）已被证明在肝癌（HCC）的肿瘤生长和转移中发挥关键作用。lncRNA FAL1 已被表明能促进各种癌症的进展。然而，lncRNA FAL1 在 HCC 中的作用还知之甚少。
方法
通过 RT-qPCR 测定 HCC 组织和细胞中 lncRNA FAL1 的表达水平。通过 MTT、集落形成、transwell、RT-qPCR 和 Western blot 研究 lncRNA FAL1 对 HCC 细胞的作用。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，还研究了 HCC 患者血清外泌体中 lncRNA FAL1 的表达水平，并通过与 HCC 细胞共培养进一步研究外泌体介导的 lncRNA FAL1 的作用。
结果
本研究首次表明，lncRNA FAL1 在 HCC 组织中上调，并在 HCC 中作为癌基因发挥作用。lncRNA FAL1 可通过竞争性结合 miR-1236 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上调，并可将 lncRNA FAL1 转移至 HCC 细胞，增强其增殖和迁移能力。
结论
综上所述，本研究表明 lncRNA FAL1 在 HCC 中作为癌基因发挥作用，可能成为未来 HCC 诊断的新型生物标志物或治疗靶点。
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