Wang Hou-Lei, Wang Hui-Ren, Liang Yun, Hu An-Nan, Enguita Francisco J, Zhou Xiao-Gang, Dong Jian
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Transl Lung Cancer Res. 2020 Dec;9(6):2411-2427. doi: 10.21037/tlcr-20-1250.
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.
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) and . 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 .
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.
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.
已知环状RNA（circRNA）参与肺癌的发生发展。然而，它们在肺腺癌脊柱转移（SM）中的作用仍不清楚。在本研究中，我们确定hsa_circ_0006571作为miR-138的海绵，在SM的发生发展中靶向沉默调节蛋白1（Sirt1）。
进行人circRNA微阵列以比较SM和肺腺癌样本。使用定量聚合酶链反应（qPCR）测定hsa_circ_0006571和miR-138的表达。通过细胞计数试剂盒-8（CCK-8）检测细胞增殖，并通过膜联蛋白V/碘化丙啶染色分析细胞凋亡。采用RNA下拉和RNA免疫沉淀（RIP）分析hsa_circ_0006571之间的相互作用。通过异种移植实验确定肿瘤转移情况。
通过circRNA微阵列和qPCR观察到hsa_circ_0006571在SM组织中显著上调。与肺腺癌相比，我们检测到SM组织中miR-138表达较低。hsa_circ_0006571沉默抑制肺癌细胞增殖和迁移，同时促进细胞凋亡。hsa_circ_0006571与miR-138相互作用以促进Sirt1表达，导致上皮-间质转化（EMT）激活。异种移植实验表明，hsa_circ_0006571的下调通过miR-138-Sirt1轴延迟肺腺癌细胞的SM。
hsa_circ_0006571通过miR-138/Sirt1途径促进肿瘤细胞迁移和侵袭。我们的观察结果表明，circRNA可能是肺腺癌SM的新型治疗靶点。
