视网膜母细胞瘤中与视神经侵犯相关的非编码RNA及其功能网络的鉴定

Identification of non-coding RNAs and their functional network associated with optic nerve invasion in retinoblastoma.

作者信息

Sun Jie, Gan Lu, Ding Jie, Ma Ruiqi, Qian Jiang, Xue Kang

机构信息

Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China.

出版信息

Heliyon. 2023 Feb 16;9(2):e13813. doi: 10.1016/j.heliyon.2023.e13813. eCollection 2023 Feb.

DOI:10.1016/j.heliyon.2023.e13813

PMID:36852072

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9958441/

Abstract

Optic nerve invasion (ONI) is an important high-risk feature and prognostic indicator of retinoblastoma (RB). Emerging evidence has revealed that non-coding RNAs (ncRNAs) play important roles in tumor perineural invasion (PNI). Nevertheless, the regulatory role of ncRNAs in the ONI of RB is poorly understood. In the current study, whole-transcriptome sequencing was performed to assess the expression profiles of ncRNAs and mRNAs in RB tissues, with or without ONI. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we predicted the biological functions of differentially expressed (DE) mRNAs. We then constructed competing endogenous RNA (ceRNA) regulatory networks based on bioinformatics analysis. The hsa_circ_0015965/lncRNA MEG3-hsa-miR-378a-5p-NOTCH1 pathway was selected and validated by real-time qPCR, western blotting, and dual luciferase reporter assays. Moreover, we demonstrated that NOTCH1 promotes the malignant progression of RB. Taken together, our results provide novel insights into the mechanism underlying optic nerve invasion in RB.

摘要

视神经侵犯（ONI）是视网膜母细胞瘤（RB）的一项重要高危特征和预后指标。新出现的证据表明，非编码RNA（ncRNAs）在肿瘤神经周围侵犯（PNI）中发挥重要作用。然而，ncRNAs在RB的ONI中的调控作用仍知之甚少。在本研究中，进行了全转录组测序，以评估有或无ONI的RB组织中ncRNAs和mRNAs的表达谱。基于基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，我们预测了差异表达（DE）mRNAs的生物学功能。然后，我们基于生物信息学分析构建了竞争性内源RNA（ceRNA）调控网络。通过实时定量PCR、蛋白质免疫印迹和双荧光素酶报告基因检测，选择并验证了hsa_circ_0015965/lncRNA MEG3-hsa-miR-378a-5p-NOTCH1通路。此外，我们证明NOTCH1促进RB的恶性进展。综上所述，我们的研究结果为RB视神经侵犯的潜在机制提供了新的见解。