Haixiang Yu, Lei Xu, Zhengjia Liu, Bo Guo, Zhifeng Han, Hua Xin
{"title":"Circ_MDM2_000139、Circ_ATF2_00418、Circ_CDC25C_002079和Circ_BIRC6_001271参与XAV939在非小细胞肺癌癌症中的功能。","authors":"Haixiang Yu, Lei Xu, Zhengjia Liu, Bo Guo, Zhifeng Han, Hua Xin","doi":"10.1155/2019/9107806","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (<b>NSCLC</b>) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells.</p><p><strong>Methods: </strong>After grouping, the NCL-H1299 cells in the treatment group were treated by 10 <i>μ</i>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.</p><p><strong>Results: </strong>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 <i>ATF2</i> 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 <i>POLR2A</i>. 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.</p><p><strong>Conclusions: </strong>Let-7 family members and <i>POLR2A</i> 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.</p>","PeriodicalId":9416,"journal":{"name":"Canadian respiratory journal","volume":"2019 ","pages":"9107806"},"PeriodicalIF":2.1000,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/9107806","citationCount":"8","resultStr":"{\"title\":\"Circ_MDM2_000139, Circ_ATF2_001418, Circ_CDC25C_002079, and Circ_BIRC6_001271 Are Involved in the Functions of XAV939 in Non-Small Cell Lung Cancer.\",\"authors\":\"Haixiang Yu, Lei Xu, Zhengjia Liu, Bo Guo, Zhifeng Han, Hua Xin\",\"doi\":\"10.1155/2019/9107806\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (<b>NSCLC</b>) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells.</p><p><strong>Methods: </strong>After grouping, the NCL-H1299 cells in the treatment group were treated by 10 <i>μ</i>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.</p><p><strong>Results: </strong>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 <i>ATF2</i> 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 <i>POLR2A</i>. 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.</p><p><strong>Conclusions: </strong>Let-7 family members and <i>POLR2A</i> 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.</p>\",\"PeriodicalId\":9416,\"journal\":{\"name\":\"Canadian respiratory journal\",\"volume\":\"2019 \",\"pages\":\"9107806\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2019-11-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1155/2019/9107806\",\"citationCount\":\"8\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Canadian respiratory journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/2019/9107806\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2019/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Canadian respiratory journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2019/9107806","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Circ_MDM2_000139, Circ_ATF2_001418, Circ_CDC25C_002079, and Circ_BIRC6_001271 Are Involved in the Functions of XAV939 in Non-Small Cell Lung Cancer.
Background: The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (NSCLC) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells.
Methods: After grouping, the NCL-H1299 cells in the treatment group were treated by 10 μM 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.
Results: 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 ATF2 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 POLR2A. 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.
Conclusions: Let-7 family members and POLR2A 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.
期刊介绍：
Canadian Respiratory Journal is a peer-reviewed, Open Access journal that aims to provide a multidisciplinary forum for research in all areas of respiratory medicine. The journal publishes original research articles, review articles, and clinical studies related to asthma, allergy, COPD, non-invasive ventilation, therapeutic intervention, lung cancer, airway and lung infections, as well as any other respiratory diseases.
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