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LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression

机译:LncRNA‐DANCR通过刺激miR‐496调节mTOR表达来促进肺腺癌的进展

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摘要

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 (ce style="fixed-case">RNA). Furthermore, the knockdown of style="fixed-case">DANCR reduced tumour volumes in vivo compared with those of the control group. In conclusion, this study showed that style="fixed-case">DANCR might be an oncogenic lnc style="fixed-case">RNA that regulates style="fixed-case">mTOR expression through directly binding to miR‐496. style="fixed-case">DANCR may be regarded as a biomarker or therapeutic target for ADC.
机译:长的非编码RNA(lncRNA)已经成为包括肿瘤发展在内的病理过程的新的重要调节剂。在这项研究中,我们证明了在肺腺癌(ADC)中分化拮抗非蛋白编码RNA(DANCR)的表达上调,并且DANCR的敲低抑制了肿瘤细胞的增殖,迁移和侵袭,并恢复了细胞凋亡。与miR‐496抑制剂共转染可逆转这些作用。萤光素酶报告基因检测表明,miR-496直接调节DANCR。此外,我们使用RNA结合蛋白免疫沉淀(RIP)和RNA下拉测定法进一步证实miR-496对DANCR的抑制是RISC依赖性的。我们的研究还表明,mTOR是miR-496的靶标,而DANCR可以通过竞争内源RNA(ce style =“ fixed-case”> RNA )来调节mTOR的表达水平。此外,与对照组相比,敲除 style =“ fixed-case”> DANCR 可以减少体内肿瘤体积。总而言之,这项研究表明 style =“ fixed-case”> DANCR 可能是调控 style =“ fixeded”的致癌lnc style =“ fixed-case”> RNA -case“> mTOR 表达式通过直接绑定到miR-496。 style =“ fixed-case”> DANCR 可以被视为ADC的生物标记或治疗靶标。

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