机构:[1]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, China.临床科室科研平台职能科室耳鼻咽喉头颈外科临床流行病与循证医学中心儿科研究所首都医科大学附属北京儿童医院[2]Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, China.临床科室职能科室耳鼻咽喉头颈外科临床流行病与循证医学中心首都医科大学附属北京儿童医院[3]Department of Surgical Oncology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, China.临床科室职能科室临床流行病与循证医学中心肿瘤外科首都医科大学附属北京儿童医院
Background: Neuroblastoma (NB) is the most common malignant tumor originating from the extracranial sympathetic nervous system in children. The molecular mechanisms underlying this disease are complex, and not completely understood. Methods: Quantitative real-time PCR (qRT-PCR) was applied to quantify the expression of miR-20a-5p and its target gene ATG7 in clinical NB tissues. The biological function of miR-20a-5p and ATG7 in SH-SY5Y cells was investigated through in vitro studies (Real-Time cell kinetic analyzer, colony formation assay, caspase-Glo 3/7 assay and western blotting). The luciferase reporter assay was conducted to verify the biological relationship between miR-20a-5p and ATG7. Results: Here we found that miR-20a-5p expression was significantly downregulated whereas its target autophagy-related gene 7 (ATG7) was increased along with clinical staging of NB progression. Correlation analysis showed that miR-20a-5p had a negative correlation trend with ATG7. In SH-SY5Y cells, forced expression of miR-20a-5p suppressed ATG7 expression, autophagy initiation and cellular proliferation while promoted apoptosis, suggesting a potential association between miR-20a-5p and ATG7. Further bioinformatic target prediction combined with protein expression and luciferase reporter assay verified that miR-20a-5p inhibited ATG7 by directly binding to its 3'-UTR, confirming the involvement of miR-20a-5p in the regulation of ATG7 in NB. Conclusions: These results clarified that miR-20a-5p inhibited cell proliferation and promoted apoptosis through negative regulation of ATG7 and thus autophagy suppression in SH-SY5Y cells. Therefore, defining the context-specific roles of autophagy in NB and regulatory mechanisms involved will be critical for developing autophagy-targeted therapeutics against NB. Both miR-20a-5p and ATG7 would be potential therapeutic targets for future NB treatment.
基金:
National Natural Science Foundation of China
(Nos. 81702463, 81472369, 81502144), Beijing Health System Top Level Technical
Personnel Training Plan (No. 20153079) and Beijing Children’s Hospital
Young Investigator Program (BCHYIPB-2016-08)
第一作者机构:[1]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, China.
共同第一作者:
通讯作者:
通讯机构:[1]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, China.[2]Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, China.
推荐引用方式(GB/T 7714):
Yongbo Yu,Jie Zhang,Yaqiong Jin,et al.MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma[J].CANCER CELL INTERNATIONAL.2018,18(1):-.doi:10.1186/s12935-017-0499-2.
APA:
Yongbo Yu,Jie Zhang,Yaqiong Jin,Yeran Yang,Jin Shi...&Xin Ni.(2018).MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma.CANCER CELL INTERNATIONAL,18,(1)
MLA:
Yongbo Yu,et al."MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma".CANCER CELL INTERNATIONAL 18..1(2018):-