Singh Nidhi, Sharma Rinku, Bose Sujoy
Department of Biotechnology, Gauhati University, Guwahati, Assam, India.
Department of Life Sciences, Shiv Nadar University, Noida, Uttar Pradesh, India.
Gastroenterol Hepatol Bed Bench. 2022;15(4):311-325. doi: 10.22037/ghfbb.v15i4.2292.
This study aimed to identify key genes, non-coding RNAs, and their possible regulatory interactions during gallbladder cancer (GBC).
The early detection of GBC, i.e. before metastasis, is restricted by our limited knowledge of molecular markers and mechanism(s) involved during carcinogenesis. Therefore, identifying important disease-associated transcriptome-level alterations can be of clinical importance.
In this study, six NCBI-GEO microarray dataseries of GBC and control tissue samples were analyzed to identify differentially expressed genes (DEGs) and non-coding RNAs {microRNAs (DEmiRNAs) and long non-coding RNAs (DElncRNAs)} with a computational meta-analysis approach. A series of bioinformatic methods were applied to enrich functional pathways, create protein-protein interaction networks, identify hub genes, and screen potential targets of DEmiRNAs and DElncRNAs. Expression and interaction data were consolidated to reveal putative DElncRNAs:DEmiRNAs:DEGs interactions.
In total, 351 DEGs (185 downregulated, 166 upregulated), 787 DEmiRNAs (299 downregulated, 488 upregulated), and 7436 DElncRNAs (3127 downregulated, 4309 upregulated) were identified. Eight genes (FGF, CDK1, RPN2, SEC61A1, SOX2, CALR, NGFR, and NCAM) were identified as hub genes. Genes associated with ubiquitin ligase activity, N-linked glycosylation, and blood coagulation were upregulated, while those for cell-cell adhesion, cell differentiation, and surface receptor-linked signaling were downregulated. DEGs-DEmiRNAs-DElncRNAs interaction network identified 46 DElncRNAs to be associated with 28 DEmiRNAs, consecutively regulating 27 DEGs. DEmiRNAs-hsa-miR-26b-5p and hsa-miR-335-5p; and DElnRNAs-LINC00657 and CTB-89H12.4 regulated the highest number of DEGs and DEmiRNAs, respectively.
The current study has identified meaningful transcriptome-level changes and gene-miRNA-lncRNA interactions during GBC and laid a platform for future studies on novel prognostic and diagnostic markers in GBC.
本研究旨在鉴定胆囊癌（GBC）发生过程中的关键基因、非编码RNA及其可能的调控相互作用。
GBC的早期检测，即在转移前的检测，受到我们对致癌过程中涉及的分子标志物和机制了解有限的限制。因此，识别重要的疾病相关转录组水平改变具有临床意义。
在本研究中，采用计算荟萃分析方法对六个GBC和对照组织样本的NCBI-GEO微阵列数据集进行分析，以鉴定差异表达基因（DEGs）和非编码RNA{微小RNA（DEmiRNAs）和长链非编码RNA（DElncRNAs）}。应用一系列生物信息学方法来富集功能通路、构建蛋白质-蛋白质相互作用网络、识别枢纽基因以及筛选DEmiRNAs和DElncRNAs的潜在靶标。整合表达和相互作用数据以揭示假定的DElncRNAs:DEmiRNAs:DEGs相互作用。
总共鉴定出351个DEGs（185个下调，166个上调）、787个DEmiRNAs（299个下调，488个上调）和7436个DElncRNAs（3127个下调，4309个上调）。八个基因（FGF、CDK1、RPN2、SEC61A1、SOX2、CALR、NGFR和NCAM）被鉴定为枢纽基因。与泛素连接酶活性、N-连接糖基化和血液凝固相关的基因上调，而与细胞-细胞粘附、细胞分化和表面受体相关信号传导相关的基因下调。DEGs-DEmiRNAs-DElncRNAs相互作用网络鉴定出与2个DEmiRNAs相关的46个DElncRNAs，依次调控27个DEGs。DEmiRNAs-hsa-miR-26b-5p和hsa-miR-335-5p；以及DElnRNAs-LINC00657和CTB-89H12.4分别调控最多数量的DEGs和DEmiRNAs。
本研究已鉴定出GBC发生过程中有意义的转录组水平变化以及基因-miRNA-lncRNA相互作用，为未来关于GBC新型预后和诊断标志物的研究奠定了平台。
