LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complex

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Long non-coding RNA LINC01296 has been shown to predict the invasiveness and poor outcomes of patients with NB. Our study validated its prognostic value and investigated the biological function and potential mechanism of LI...

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Main Authors: Jing Wang, Zuopeng Wang, Weihong Lin, Qilei Han, Hanlei Yan, Wei Yao, Rui Dong, Deshui Jia, Kuiran Dong, Kai Li
Format: Article
Language:English
Published: Elsevier 2022-03-01
Series:Molecular Therapy: Oncolytics
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2372770522000249
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author Jing Wang
Zuopeng Wang
Weihong Lin
Qilei Han
Hanlei Yan
Wei Yao
Rui Dong
Deshui Jia
Kuiran Dong
Kai Li
author_facet Jing Wang
Zuopeng Wang
Weihong Lin
Qilei Han
Hanlei Yan
Wei Yao
Rui Dong
Deshui Jia
Kuiran Dong
Kai Li
author_sort Jing Wang
collection DOAJ
description Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Long non-coding RNA LINC01296 has been shown to predict the invasiveness and poor outcomes of patients with NB. Our study validated its prognostic value and investigated the biological function and potential mechanism of LINC01296 regulating NB. Results illuminated that LINC01296 expression was significantly correlated with unfavorable prognosis and malignant clinical features according to the public NB database. We identified that silencing LINC01296 repressed NB cell proliferation and migration and promoted apoptosis. Moreover, LINC01296 knockdown inhibited tumor growth in vivo. The opposite results were observed through the dCas9 Synergistic Activation Mediator System (dCas9/SAM) activating LINC01296. Mechanistically, we revealed that LINC01296 could directly bind to nucleolin (NCL), forming a complex that activated SRY-box transcription factor 11 (SOX11) gene transcription and accelerated tumor progression. In conclusion, our findings uncover a crucial role of the LINC01296-NCL-SOX11 complex in NB tumorigenesis and may serve as a prognostic biomarker and effective therapeutic target for NB.
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spelling doaj.art-6a4c96877aa54cda83e5a53d14a376682022-12-21T18:35:26ZengElsevierMolecular Therapy: Oncolytics2372-77052022-03-0124834848LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complexJing Wang0Zuopeng Wang1Weihong Lin2Qilei Han3Hanlei Yan4Wei Yao5Rui Dong6Deshui Jia7Kuiran Dong8Kai Li9Department of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, ChinaDepartment of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, ChinaDepartment of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, ChinaDepartment of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, ChinaDepartment of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, ChinaDepartment of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, ChinaDepartment of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, ChinaLaboratory of Cancer Genomics and Biology, Department of Urology, and Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Corresponding author Deshui Jia, Laboratory of Cancer Genomics and Biology, Department of Urology, and Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.Department of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; Corresponding author Kuiran Dong, Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Shanghai 201102, P.R. China.Department of Pediatric Surgery, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; Corresponding author Kai Li, Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Shanghai 201102, P.R. China.Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Long non-coding RNA LINC01296 has been shown to predict the invasiveness and poor outcomes of patients with NB. Our study validated its prognostic value and investigated the biological function and potential mechanism of LINC01296 regulating NB. Results illuminated that LINC01296 expression was significantly correlated with unfavorable prognosis and malignant clinical features according to the public NB database. We identified that silencing LINC01296 repressed NB cell proliferation and migration and promoted apoptosis. Moreover, LINC01296 knockdown inhibited tumor growth in vivo. The opposite results were observed through the dCas9 Synergistic Activation Mediator System (dCas9/SAM) activating LINC01296. Mechanistically, we revealed that LINC01296 could directly bind to nucleolin (NCL), forming a complex that activated SRY-box transcription factor 11 (SOX11) gene transcription and accelerated tumor progression. In conclusion, our findings uncover a crucial role of the LINC01296-NCL-SOX11 complex in NB tumorigenesis and may serve as a prognostic biomarker and effective therapeutic target for NB.http://www.sciencedirect.com/science/article/pii/S2372770522000249neuroblastomapediatric cancerlong non-coding RNALINC01296NCLSOX11
spellingShingle Jing Wang
Zuopeng Wang
Weihong Lin
Qilei Han
Hanlei Yan
Wei Yao
Rui Dong
Deshui Jia
Kuiran Dong
Kai Li
LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complex
Molecular Therapy: Oncolytics
neuroblastoma
pediatric cancer
long non-coding RNA
LINC01296
NCL
SOX11
title LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complex
title_full LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complex
title_fullStr LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complex
title_full_unstemmed LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complex
title_short LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complex
title_sort linc01296 promotes neuroblastoma tumorigenesis via the ncl sox11 regulatory complex
topic neuroblastoma
pediatric cancer
long non-coding RNA
LINC01296
NCL
SOX11
url http://www.sciencedirect.com/science/article/pii/S2372770522000249
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