Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China.
Can Respir J. 2019 Nov 27;2019:9107806. doi: 10.1155/2019/9107806. eCollection 2019.
The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer () cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells.
After grouping, the NCL-H1299 cells in the treatment group were treated by 10 M XAV939 for 12 h. RNA-sequencing was performed, and then the differentially expressed circRNAs (DE-circRNAs) were analyzed by the edgeR package. Using the clusterprofiler package, enrichment analysis for the hosting genes of the DE-circRNAs was performed. Using Cytoscape software, the miRNA-circRNA regulatory network was built for the disease-associated miRNAs and the DE-circRNAs. The DE-circRNAs that could translate into proteins were predicted using circBank database and IRESfinder tool. Finally, the transcription factor (TF)-circRNA regulatory network was built by Cytoscape software. In addition, A549 and HCC-827 cell treatment with XAV939 were used to verify the relative expression levels of key DE-circRNAs.
There were 106 DE-circRNAs (including 61 upregulated circRNAs and 45 downregulated circRNAs) between treatment and control groups. Enrichment analysis for the hosting genes of the DE-circRNAs showed that was enriched in the TNF signaling pathway. Disease association analysis indicated that 8 circRNAs (including circ_MDM2_000139, circ_ATF2_001418, circ_CDC25C_002079, and circ_BIRC6_001271) were correlated with NSCLC. In the miRNA-circRNA regulatory network, let-7 family members⟶circ_MDM2_000139, miR-16-5p/miR-134-5p⟶circ_ATF2_001418, miR-133b⟶circ_BIRC6_001271, and miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 regulatory pairs were involved. A total of 47 DE-circRNAs could translate into proteins. Additionally, circ_MDM2_000139 was targeted by the TF . The verification test showed that the relative expression levels of circ_MDM2_000139, circ_CDC25C_002079, circ_ATF2_001418, and circ_DICER1_000834 in A549 and HCC-827 cell treatment with XAV939 were downregulated comparing with the control.
Let-7 family members and targeting circ_MDM2_000139, miR-16-5p/miR-134-5p targeting circ_ATF2_001418, miR-133b targeting circ_BIRC6_001271, and miR-221-3p/miR-222-3p targeting circ_CDC25C_002079 might be related to the mechanism in the treatment of NSCLC by XAV939.
小分子抑制剂 XAV939 能够抑制非小细胞肺癌（NSCLC）细胞的增殖并促进其凋亡。本研究旨在鉴定 XAV939 处理的 NSCLC 细胞中的关键环状 RNA（circRNA）和 microRNA（miRNA）。
分组后，用 10 μM XAV939 处理实验组的 NCL-H1299 细胞 12 小时。进行 RNA 测序，然后使用 edgeR 包分析差异表达的 circRNAs（DE-circRNAs）。使用 clusterprofiler 包对 DE-circRNAs 的宿主基因进行富集分析。利用 Cytoscape 软件构建与疾病相关的 miRNA 和 DE-circRNAs 的 miRNA-circRNA 调控网络。使用 circBank 数据库和 IRESfinder 工具预测可翻译为蛋白质的 DE-circRNAs。最后，使用 Cytoscape 软件构建转录因子（TF）-circRNA 调控网络。此外，使用 XAV939 处理 A549 和 HCC-827 细胞以验证关键 DE-circRNAs 的相对表达水平。
处理组和对照组之间有 106 个 DE-circRNAs（包括 61 个上调的 circRNAs 和 45 个下调的 circRNAs）。DE-circRNAs 的宿主基因富集分析表明，TNF 信号通路富集。疾病关联分析表明，8 个 circRNAs（包括 circ_MDM2_000139、circ_ATF2_001418、circ_CDC25C_002079 和 circ_BIRC6_001271）与 NSCLC 相关。在 miRNA-circRNA 调控网络中，let-7 家族成员⟶circ_MDM2_000139、miR-16-5p/miR-134-5p⟶circ_ATF2_001418、miR-133b⟶circ_BIRC6_001271 和 miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 调控对参与其中。共有 47 个 DE-circRNAs 可以翻译为蛋白质。此外，circ_MDM2_000139 受 TF 的靶向调控。验证实验表明，XAV939 处理的 A549 和 HCC-827 细胞中 circ_MDM2_000139、circ_CDC25C_002079、circ_ATF2_001418 和 circ_DICER1_000834 的相对表达水平均低于对照组。
let-7 家族成员和 靶向 circ_MDM2_000139、miR-16-5p/miR-134-5p 靶向 circ_ATF2_001418、miR-133b 靶向 circ_BIRC6_001271 和 miR-221-3p/miR-222-3p 靶向 circ_CDC25C_002079 可能与 XAV939 治疗 NSCLC 的机制有关。
