Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway
Abstract Background Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on N...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-019-0968-x |
| _version_ | 1818154030656913408 |
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| author | Huan-yu Zhang Mao-qing Xing Jing Guo Jin-chuan Zhao Xin Chen Zhong Jiang Hong Zhang Qian Dong |
| author_facet | Huan-yu Zhang Mao-qing Xing Jing Guo Jin-chuan Zhao Xin Chen Zhong Jiang Hong Zhang Qian Dong |
| author_sort | Huan-yu Zhang |
| collection | DOAJ |
| description | Abstract Background Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved. Methods Through mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo. Results We identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain‐derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence. Conclusion Overall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB. |
| first_indexed | 2024-12-11T14:20:02Z |
| format | Article |
| id | doaj.art-c3c72e90e89642098b128f850a0bafd1 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-11T14:20:02Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-c3c72e90e89642098b128f850a0bafd12022-12-22T01:02:57ZengBMCCancer Cell International1475-28672019-11-0119111210.1186/s12935-019-0968-xLong noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathwayHuan-yu Zhang0Mao-qing Xing1Jing Guo2Jin-chuan Zhao3Xin Chen4Zhong Jiang5Hong Zhang6Qian Dong7Department of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityAbstract Background Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved. Methods Through mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo. Results We identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain‐derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence. Conclusion Overall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.http://link.springer.com/article/10.1186/s12935-019-0968-xNeuroblastomalncRNA DLX6-AS1ProliferationInvasion and migrationmiR-107Brain‐derived neurotrophic factor |
| spellingShingle | Huan-yu Zhang Mao-qing Xing Jing Guo Jin-chuan Zhao Xin Chen Zhong Jiang Hong Zhang Qian Dong Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway Cancer Cell International Neuroblastoma lncRNA DLX6-AS1 Proliferation Invasion and migration miR-107 Brain‐derived neurotrophic factor |
| title | Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway |
| title_full | Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway |
| title_fullStr | Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway |
| title_full_unstemmed | Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway |
| title_short | Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway |
| title_sort | long noncoding rna dlx6 as1 promotes neuroblastoma progression by regulating mir 107 bdnf pathway |
| topic | Neuroblastoma lncRNA DLX6-AS1 Proliferation Invasion and migration miR-107 Brain‐derived neurotrophic factor |
| url | http://link.springer.com/article/10.1186/s12935-019-0968-x |
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