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BRD4在胃癌进展中的表达及其与miR-26a-3p、DLG5-AS1和JMJD1C-AS1长链非编码RNA的调控相互作用。

BRD4 expression and its regulatory interaction with miR-26a-3p, DLG5-AS1, and JMJD1C-AS1 lncRNAs in gastric cancer progression.

作者信息

Ahmadpour Youshanlui Mahya, Yari Amirhossein, Bahojb Mahdavi Seyedeh Zahra, Amini Mohammad, Baradaran Behzad, Ahangar Ramin, Pourbagherian Omid, Mokhtarzadeh Amir Ali

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Discov Oncol. 2024 Aug 16;15(1):356. doi: 10.1007/s12672-024-01230-7.

DOI:10.1007/s12672-024-01230-7
PMID:39152304
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11329449/
Abstract

Gastric cancer remains a significant health challenge despite advancements in diagnosis and treatment. Early detection is critical to reducing mortality, necessitating the investigation of molecular mechanisms underlying gastric cancer progression. This study focuses on BRD4 expression and its correlation with miR-26a-3p, DLG5-AS1, and JMJD1C-AS1 lncRNAs in gastric cancer. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed significant upregulation of BRD4 in gastric cancer tissues compared to normal tissues, correlating negatively with miR-26a-3p and positively with DLG5-AS1 and JMJD1C-AS1 lncRNAs. Quantitative RT-PCR confirmed these findings in 25 gastric cancer tissue samples and 25 normal samples. BRD4's overexpression was associated with reduced survival rates and older patient age. MiR-26a-3p, a known tumor suppressor, showed decreased expression in gastric cancer tissues, with ROC analysis suggesting it, alongside BRD4, as a potential diagnostic biomarker. Additionally, bioinformatics predicted miR-26a-3p's interaction with BRD4 mRNA. Upregulated lncRNAs DLG5-AS1 and JMJD1C-AS1 likely act as competing endogenous RNAs, sponging miR-26a-3p, thus promoting BRD4 dysregulation. These lncRNAs have not been previously studied in gastric cancer. The findings propose a novel BRD4/lncRNA/miRNA regulatory axis in gastric cancer, highlighting the potential of BRD4, DLG5-AS1, and JMJD1C-AS1 as biomarkers for early diagnosis. Further studies with larger sample sizes and in vivo and in vitro experiments are needed to elucidate this regulatory mechanism's role in gastric cancer progression.

摘要

尽管在胃癌的诊断和治疗方面取得了进展，但胃癌仍然是一个重大的健康挑战。早期检测对于降低死亡率至关重要，因此有必要研究胃癌进展的分子机制。本研究聚焦于BRD4在胃癌中的表达及其与miR-26a-3p、DLG5-AS1和JMJD1C-AS1长链非编码RNA（lncRNA）的相关性。对癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据集的分析显示，与正常组织相比，胃癌组织中BRD4显著上调，与miR-26a-3p呈负相关，与DLG5-AS1和JMJD1C-AS1 lncRNA呈正相关。定量逆转录聚合酶链反应（qRT-PCR）在25个胃癌组织样本和25个正常样本中证实了这些发现。BRD4的过表达与生存率降低和患者年龄较大有关。已知的肿瘤抑制因子miR-26a-3p在胃癌组织中表达降低，ROC分析表明它与BRD4一起可作为潜在的诊断生物标志物。此外，生物信息学预测了miR-26a-3p与BRD4 mRNA的相互作用。上调的lncRNA DLG5-AS1和JMJD1C-AS1可能作为竞争性内源性RNA，吸附miR-26a-3p，从而促进BRD4失调。此前尚未在胃癌中对这些lncRNA进行研究。这些发现提出了一种新的胃癌BRD4/lncRNA/miRNA调控轴，突出了BRD4、DLG5-AS1和JMJD1C-AS1作为早期诊断生物标志物的潜力。需要进行更大样本量的进一步研究以及体内和体外实验，以阐明这种调控机制在胃癌进展中的作用。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d330/11329449/3e4194a79789/12672_2024_1230_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d330/11329449/7071be345caf/12672_2024_1230_Fig9_HTML.jpg
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A Novel Oxidative Stress-Related lncRNA Signature That Predicts the Prognosis and Tumor Immune Microenvironment of Breast Cancer.
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