Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma.
Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma.
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长非编码RNA DANCR作为竞争性内源RNA，通过诱骗骨肉瘤中的miR-335-5p和miR-1972促进ROCK1介导的增殖和转移
DOI：
10.1186/s12943-018-0837-6
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发表时间：
2018-05-12
期刊：
影响因子：
37.3
通讯作者：
Lu Z
中科院分区：
文献类型：
--
作者：
Wang Y;Zeng X;Wang N;Zhao W;Zhang X;Teng S;Zhang Y;Lu Z
背景越来越多的证据表明非编码RNA（non-coding RNAs，ncRNA）包括长链非编码RNA（long non-coding RNAs，lncRNA）和微小RNA（microRNAs，miRNAs）在骨肉瘤（osteosarcoma，OS）中起着重要的调控作用。以前我们报道了一个转移相关基因ROCK 1（Rho associated coiled-coil containing protein kinase 1，ROCK 1）受microRNA-335 - 5p（miR-335 - 5p）负调控，并在骨肉瘤中作为癌基因发挥作用。方法采用qRT-PCR和ISH方法检测骨肉瘤组织中分化拮抗非蛋白编码RNA（DANCR）和miR-335 - 5p/miR-1972的表达。CCK-8/EDU法和transwell法分别检测骨肉瘤细胞增殖和迁移/侵袭能力的变化。通过qRT-PCR测定和蛋白质印迹测定检查ROCK1表达变化。通过双荧光素酶报告基因测定和RIP测定验证miR-335 - 5p/miR-1972与ROCK1或DANCR之间的靶向结合作用。在体内实验，包括裸形成试验，以及CT扫描被施加到检测肿瘤的生长和转移的变化，在动物level.ResultsIn本研究中，发现在骨肉瘤组织标本和骨肉瘤细胞系的DNACR升高，和升高的DNACR是密切相关的临床患者预后不良。功能实验表明，抑制DANCR抑制ROCK 1介导的骨肉瘤细胞的增殖和转移。western blot和qRT-PCR检测结果显示，DANCR通过与miR-335 - 5p和miR-1972的相互作用调控ROCK1。进一步的细胞行为学实验表明，DNACR通过诱骗miR-335 - 5p和miR-1972促进ROCK1介导的增殖和转移。结论LncRNA DANCR在骨肉瘤中作为癌基因发挥作用，并通过竞争内源性RNA（ceRNA）促进ROCK 1介导的增殖和转移。
BackgroundAccumulating evidences indicate that non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as crucial regulators in osteosarcoma (OS). Previously, we reported that Rho associated coiled-coil containing protein kinase 1 (ROCK1), a metastatic-related gene was negatively regulated by microRNA-335-5p (miR-335-5p) and work as an oncogene in osteosarcoma. Whether any long non-coding RNAs participate in the upstream of miR-335-5p/ROCK1 axial remains unclear.MethodsExpression of differentiation antagonizing non-protein coding RNA (DANCR) and miR-335-5p/miR-1972 in osteosarcoma tissues were determined by a qRT-PCR assay and an ISH assay. Osteosarcoma cells’ proliferation and migration/invasion ability changes were measured by a CCK-8/EDU assay and a transwell assay respectively. ROCK1 expression changes were checked by a qRT-PCR assay and a western blot assay. Targeted binding effects between miR-335-5p/miR-1972 and ROCK1 or DANCR were verified by a dual luciferase reporter assay and a RIP assay. In vivo experiments including a nude formation assay as well as a CT scan were applied to detect tumor growth and metastasis changes in animal level.ResultsIn the present study, an elevated DNACR was found in osteosarcoma tissue specimens and in osteosarcoma cell lines, and the elevated DNACR was closely correlated with poor prognosis in clinical patients. Functional experiments illustrated that a depression of DANCR suppressed ROCK1-mediated proliferation and metastasis in osteosarcoma cells. The results of western blot assays and qRT-PCR assays revealed that DANCR regulated ROCK1 via crosstalk with miR-335-5p and miR-1972. Further cellular behavioral experiments demonstrated that DNACR promoted ROCK1-meidated proliferation and metastasis through decoying both miR-335-5p and miR-1972. Finally, the outcomes of in vivo animal models showed that DANCR promoted tumor growth and lung metastasis of osteosarcoma.ConclusionsLncRNA DANCR work as an oncogene and promoted ROCK1-mediated proliferation and metastasis through acting as a competing endogenous RNA (ceRNA) in osteosarcoma.
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