Department of Respiratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Respiratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China.
J Cell Mol Med. 2018 Mar;22(3):1527-1537. doi: 10.1111/jcmm.13420. Epub 2017 Dec 20.
Long non-coding RNAs (lncRNAs) have emerged as new and important regulators of pathological processes including tumour development. In this study, we demonstrated that differentiation antagonizing non-protein coding RNA (DANCR) was up-regulated in lung adenocarcinoma (ADC) and that the knockdown of DANCR inhibited tumour cell proliferation, migration and invasion and restored cell apoptosis rescued; cotransfection with a miR-496 inhibitor reversed these effects. Luciferase reporter assays showed that miR-496 directly modulated DANCR; additionally, we used RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays to further confirm that the suppression of DANCR by miR-496 was RISC-dependent. Our study also indicated that mTOR was a target of miR-496 and that DANCR could modulate the expression levels of mTOR by working as a competing endogenous RNA (ceRNA). Furthermore, the knockdown of DANCR reduced tumour volumes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regulates mTOR expression through directly binding to miR-496. DANCR may be regarded as a biomarker or therapeutic target for ADC.
长链非编码 RNA（lncRNA）已成为包括肿瘤发生在内的病理过程的新的重要调控因子。在本研究中，我们证明了分化拮抗非蛋白编码 RNA（DANCR）在肺腺癌（ADC）中上调，并且 DANCR 的敲低抑制了肿瘤细胞增殖、迁移和侵袭，并恢复了细胞凋亡；共转染 miR-496 抑制剂逆转了这些作用。荧光素酶报告基因检测表明 miR-496 直接调控 DANCR；此外，我们使用 RNA 结合蛋白免疫沉淀（RIP）和 RNA 下拉实验进一步证实 miR-496 通过 RISC 依赖性抑制 DANCR。我们的研究还表明，mTOR 是 miR-496 的靶标，DANCR 可以通过作为竞争内源性 RNA（ceRNA）来调节 mTOR 的表达水平。此外，与对照组相比，DANCR 的敲低可减少体内肿瘤体积。总之，本研究表明 DANCR 可能是一种致癌 lncRNA，通过直接与 miR-496 结合来调节 mTOR 的表达。DANCR 可作为 ADC 的生物标志物或治疗靶点。
