Feng Xiaofen, Gong Jian, Li Qian, Xing Chao, Pan Jiandong, Zou Ruitao, Zheng Liya, Chen Feng
Pediatric Fundus Department, School of Optometry & Ophthalmology, Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
Exp Ther Med. 2021 Dec;22(6):1447. doi: 10.3892/etm.2021.10882. Epub 2021 Oct 14.
Retinoblastoma (RB), the most common intraocular malignancy, typically occurs in pediatric patients under the age of 6 years. The present study aimed to explore the long noncoding RNA (lncRNA) expression profile in RB and identify novel lncRNA biomarkers to facilitate the investigation of molecular mechanisms of RB and improve clinical therapy. Raw microarray data for the comparison of gene expression between three RB and three adjacent normal tissue samples were downloaded from Gene Expression Omnibus (dataset no. GSE111168). After identification of differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) in RB, functional enrichment analyses and a DEL-DEM weighted correlation network analysis were performed. A total of 3,915 DELs (1,774 upregulated and 2,141 downregulated) and 3,715 DEMs (1,492 upregulated and 2,223 downregulated) were identified in RB. The DEL-targeted DEMs were highly enriched by genes involved in hexose transport, muscle tissue morphogenesis, the stereocilium membrane, endothelin B receptor binding and γ-filamin/ABP-L, α-actinin and telethonin binding protein of the Z-disc binding. Furthermore, associations of the DELs and DEMs with several pathways were determined, including PI3K/AKT, Hippo and cancer signaling, as well as extracellular matrix-receptor interaction pathways. Coexpression network analysis revealed that the top three DELs, lnc-DAZ1-161, lnc-HDAC7-21 and lnc-OR52A1-55, formed coexpression modules with 181, 156 and 210 DEMs, respectively. In addition, the top three DEMs, namely EIF1AY, GSTM1 and NLRP11, formed coexpression modules with 33, 50 and 41 DELs, respectively. Validation using reverse transcription-quantitative PCR indicated that the expression of representative lncRNAs (lnc-DAZ1-161 and lnc-HDAC7-21) in RB cells was consistent with that in RB tissues in the database, while the expression of lnc-OR52A1-55 was not consistent with the database. These results suggested that the aberrant lncRNA expression profile in RB is related to the differential regulation of numerous physiological and pathological processes. The lncRNA and mRNA profiles in RB identified may provide novel targets for the investigation of its molecular mechanisms and thus lead to improvements in clinical therapy for RB.
视网膜母细胞瘤（RB）是最常见的眼内恶性肿瘤，通常发生于6岁以下的儿科患者。本研究旨在探索RB中的长链非编码RNA（lncRNA）表达谱，并鉴定新的lncRNA生物标志物，以促进对RB分子机制的研究并改善临床治疗。从基因表达综合数据库（数据集编号GSE111168）下载了用于比较三个RB组织样本和三个相邻正常组织样本之间基因表达的原始微阵列数据。在鉴定出RB中差异表达的lncRNA（DEL）和差异表达的mRNA（DEM）后，进行了功能富集分析和DEL-DEM加权相关网络分析。在RB中总共鉴定出3915个DEL（1774个上调和2141个下调）和3715个DEM（1492个上调和2223个下调）。DEL靶向的DEM在参与己糖转运、肌肉组织形态发生、静纤毛膜、内皮素B受体结合以及γ-丝动蛋白/ABP-L、α-辅肌动蛋白和Z盘结合的肌联蛋白结合蛋白的基因中高度富集。此外，还确定了DEL和DEM与多种信号通路的关联，包括PI3K/AKT、Hippo和癌症信号通路，以及细胞外基质-受体相互作用通路。共表达网络分析显示，排名前三的DEL，即lnc-DAZ1-161、lnc-HDAC7-21和lnc-OR52A1-55，分别与181、156和210个DEM形成共表达模块。此外，排名前三的DEM，即EIF1AY、GSTM1和NLRP11，分别与33、50和41个DEL形成共表达模块。使用逆转录定量PCR进行的验证表明，RB细胞中代表性lncRNA（lnc-DAZ1-161和lnc-HDAC7-21）的表达与数据库中RB组织的表达一致，而lnc-OR52A1-55的表达与数据库不一致。这些结果表明，RB中异常的lncRNA表达谱与众多生理和病理过程的差异调节有关。在RB中鉴定出的lncRNA和mRNA谱可能为其分子机制的研究提供新的靶点，从而改善RB的临床治疗。
