小核仁RNA宿主基因4在胃癌中的表达及调控作用

Expression and Regulatory Roles of Small Nucleolar RNA Host Gene 4 in Gastric Cancer.

作者信息

Pourghasem Navid, Ghorbanzadeh Shadi, Nejatizadeh Azim

机构信息

Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

出版信息

Curr Protein Pept Sci. 2023;24(9):767-779. doi: 10.2174/1389203724666230810094548.

DOI:10.2174/1389203724666230810094548

PMID:37565552

Abstract

AIMS

The role of SNHG4 in the initiation and development of gastric cancer.

BACKGROUND

Gastric cancer is one of the leading causes of cancer death worldwide. Studies have shown that lncRNAs have a regulatory function in human diseases, particularly cancers. Small nuclear RNA host gene 4 (SNHG4) has been known as an oncogenic long noncoding RNA (lncRNA) in various cancers, and its dysregulation can lead to tumorigenesis and cancer progression.

OBJECTIVE

Alteration of SNHG4 expression in gastric cancer and its correlation with clinical features of patients with stomach cancer; also, the accomplishment of bioinformatic analysis to find the potential pathways which could be impressed by changes in SNHG4 RNA expression.

METHODS

The present study aims to determine the molecular mechanism of SNHG4 and the effects of its expression on the development of GC. Based on the bioinformatics investigations, we studied gene expression analysis, Kaplan-Meier survival, Gene ontology (GO), KEGG pathway enrichment, microRNA targets, transcription factor targets, and proteins interacting with SNHG4. During the experimental phase, SNHG4 expression was examined by quantitative real-time PCR (qRTPCR) in 40 paired gastric adenocarcinoma tissues and normal neighboring tissues. Also, we investigated the correlation between SNHG4 expression and patients' clinicopathological characteristics.

RESULTS

Increased SNHG4 expression was detected in GC tissues, which is significantly associated with the TNM stage, grade group, tumor size, and metastatic status. Evaluation survival analysis demonstrated that overexpression of SNHG4 in GC tissues is remarkably related to poor overall survival (OS). SNHG4 is closely related to miR-490 and E2F family transcription factors. GO analysis suggested the possible role of SNHG4 in cell-cell adhesion, and KEGG enrichment analysis revealed that SNHG4 could be associated with the gastric cancer signaling pathway. ELAVL1 and IGF2BP2 have the highest number of SNHG4 target sites, and these proteins are involved in the PI3K-Akt-mTOR and ERK-MAPK signaling pathways.

CONCLUSION

Based on our results, we conclude that SNHG4 may have a function in GC development by regulating tumor-related signaling pathways.

摘要

目的

探讨SNHG4在胃癌发生发展中的作用。

背景

胃癌是全球癌症死亡的主要原因之一。研究表明，长链非编码RNA（lncRNA）在人类疾病尤其是癌症中具有调节功能。小核RNA宿主基因4（SNHG4）在多种癌症中被认为是一种致癌性长链非编码RNA，其失调可导致肿瘤发生和癌症进展。

目的

检测胃癌中SNHG4表达的变化及其与胃癌患者临床特征的相关性；同时，通过生物信息学分析找出可能受SNHG4 RNA表达变化影响的潜在途径。

方法

本研究旨在确定SNHG4的分子机制及其表达对胃癌发展的影响。基于生物信息学研究，我们进行了基因表达分析、Kaplan-Meier生存分析、基因本体（GO）分析、KEGG通路富集分析、微小RNA靶点分析、转录因子靶点分析以及与SNHG4相互作用的蛋白质分析。在实验阶段，采用定量实时聚合酶链反应（qRT-PCR）检测40对胃腺癌组织及相邻正常组织中SNHG4的表达。此外，我们还研究了SNHG4表达与患者临床病理特征之间的相关性。

结果

在胃癌组织中检测到SNHG4表达增加，这与TNM分期、分级组、肿瘤大小和转移状态显著相关。生存分析表明，胃癌组织中SNHG4的过表达与总体生存期（OS）较差显著相关。SNHG4与miR-490和E2F家族转录因子密切相关。GO分析提示SNHG4在细胞间黏附中可能发挥作用，KEGG富集分析显示SNHG4可能与胃癌信号通路相关。ELAVL1和IGF2BP2具有最多的SNHG4靶点，这些蛋白质参与PI3K-Akt-mTOR和ERK-MAPK信号通路。