Hsa_circ_0006571 promotes spinal metastasis through sponging microRNA-138 to regulate sirtuin 1 expression in lung adenocarcinoma.
Hsa_circ_0006571 promotes spinal metastasis through sponging microRNA-138 to regulate sirtuin 1 expression in lung adenocarcinoma.
复制标题
Hsa_circ_0006571 通过海绵 microRNA-138 调节肺腺癌中 Sirtuin 1 的表达促进脊柱转移
DOI：
10.21037/tlcr-20-1250
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发表时间：
2020-12
影响因子：
4
通讯作者：
Dong J
中科院分区：
文献类型：
--
作者：
Wang HL;Wang HR;Liang Y;Hu AN;Enguita FJ;Zhou XG;Dong J
背景已知环状RNA（circRNA）参与肺癌。然而，它们在肺腺癌脊柱转移（SM）中的作用仍然是难以捉摸的。在这项研究中，我们确定hsa_circ_0006571作为miR-138的海绵，其靶向沉默调节蛋白1（Sirt 1）在SM的发展。方法应用人circRNA微阵列技术比较SM和肺腺癌标本。使用定量聚合酶链反应（qPCR）在体外和体内测定hsa_circ_0006571和miR-138的表达。CCK-8法检测细胞增殖，Annexin V/PI双染法检测细胞凋亡。使用RNA-下拉和RNA免疫沉淀（RIP）来分析hsa_circ_0006571之间的相互作用。通过体内异种移植实验确定肿瘤转移。结果CircRNA微阵列和qPCR检测结果显示Hsa_circ_0006571在SM组织中表达显著上调。我们检测到与肺腺癌相比，SM组织中miR-138的表达较低。Hsa_circ_0006571沉默抑制肺癌细胞增殖和迁移，同时促进凋亡。Hsa_circ_0006571与miR-138相互作用促进Sirt 1的表达，导致上皮-间充质转化（EMT）的激活。异种移植实验表明，下调hsa_circ_0006571通过miR-138-Sirt 1轴延迟肺腺癌细胞的SM。结论Hsa_circ_0006571通过miR-138/Sirt 1途径促进肿瘤细胞迁移和侵袭。我们的观察表明，circRNA可能是肺腺癌SM的新的治疗靶点。
Background Circular RNAs (circRNAs) are known to participate in lung cancer. However, their role in spinal metastasis (SM) of lung adenocarcinoma remains elusive. In this study, we determined that hsa_circ_0006571 serves as a sponge for miR-138, which targets sirtuin 1 (Sirt1) in the development of SM. Methods A human circRNA microarray was performed to compare SM and lung adenocarcinoma samples. The expression of hsa_circ_0006571 and miR-138 was determined using quantitative polymerase chain reaction (qPCR) in vitro and in vivo. Cell proliferation was performed by Cell Counting Kit-8 (CCK-8) and apoptosis was analyzed by Annexin V/PI staining. RNA-pulldown and RNA immunoprecipitation (RIP) were used to analyze the interaction between hsa_circ_0006571. Tumor metastasis was determined through a xenograft experiment in vivo. Results Hsa_circ_0006571 was observed to be significantly upregulated in SM tissues through circRNA microarray and qPCR. We detected a lower expression of miR-138 in SM tissues compared with lung adenocarcinoma. Hsa_circ_0006571 silencing suppressed lung cancer cell proliferation and migration while promoting apoptosis. Hsa_circ_0006571 interacted with miR-138 to promote expression of Sirt1, leading to activation of epithelial-mesenchymal transition (EMT). Xenograft experiments showed that downregulation of hsa_circ_0006571 delayed the SM of lung adenocarcinoma cells via the miR-138-Sirt1 axis. Conclusions Hsa_circ_0006571 promoted tumor cell migration and invasion via the miR-138/Sirt1 pathway. Our observations indicate that circRNAs are possible novel therapeutic targets for SM of lung adenocarcinoma.