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基于生物信息学和实验研究的长链非编码RNA LINC00839在口腔鳞状细胞癌中的作用

The role of long non-coding RNA LINC00839 in oral squamous cell carcinoma based on bioinformatics and experimental research.

作者信息

Kalantary-Charvadeh Ashkan, Morovat Saman, Aslani Somayeh, Ziamajidi Nasrin, Emami Razavi Amirnader, Abbasalipourkabir Roghayeh

机构信息

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Sci Rep. 2024 Dec 30;14(1):31817. doi: 10.1038/s41598-024-82922-6.

DOI:10.1038/s41598-024-82922-6
PMID:39738469
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11686358/
Abstract

This study explores the role of LINC00839 and its potential interaction with the miR-195-5p/cyclin E1 (CCNE1) axis in oral squamous cell carcinoma (OSCC). Using The Cancer Genome Atlas, we analyzed lncRNA, miRNA, and mRNA sequencing data for OSCC. Different online tools were applied to detect lncRNA-related miRNAs and their target mRNAs, forming a lncRNA/miRNA/mRNA axis. Co-expression analysis determined the correlation between lncRNA and mRNA expression. Afterward, protein-protein interaction network and functional enrichment analyses disclosed the biological activity of target genes. The expression and correlations of LINC00839, miR-195-5p, and CCNE1 were examined in 30 pairs of OSCC and noncancerous tissues. A Chi-square test was used to determine clinicopathological associations, and ROC analysis estimated diagnostic value. A total of 66 differentially expressed lncRNAs, 80 miRNAs, and 1149 mRNAs were identified in OSCC versus non-tumor samples. After filtering lncRNAs based on novelty, and predicting lncRNA-miRNA, and miRNA-mRNA interactions, the LINC00839/miR-195-5p/CCNE1 axis was discovered. RT-qPCR showed upregulation of LINC00839 and CCNE1 was accompanied by the downregulation of miR-195-5p. A significant positive correlation was observed between LINC00839 and CCNE1 mRNA expression, along with a significant negative correlation between LINC00839 and miR-195-5p expression. Moreover, increased LINC00839 was associated with tumor grade and lymph node status, while decreased miR-195-5p was correlated with lymph, depth, and vascular invasion (p < 0.05). The combined ROC curve demonstrated a significant area under the curve of 0.93. This discovery reveals a novel regulatory mechanism underlying OSCC tumorigenesis and may provide effective diagnosis and potential therapeutic targets to cure this devastating cancer.

摘要

本研究探讨了LINC00839在口腔鳞状细胞癌(OSCC)中的作用及其与miR-195-5p/细胞周期蛋白E1(CCNE1)轴的潜在相互作用。利用癌症基因组图谱,我们分析了OSCC的lncRNA、miRNA和mRNA测序数据。应用不同的在线工具检测lncRNA相关的miRNA及其靶mRNA,形成lncRNA/miRNA/mRNA轴。共表达分析确定了lncRNA与mRNA表达之间的相关性。随后,蛋白质-蛋白质相互作用网络和功能富集分析揭示了靶基因的生物学活性。检测了30对OSCC组织和癌旁组织中LINC00839、miR-195-5p和CCNE1的表达及相关性。采用卡方检验确定临床病理相关性,ROC分析评估诊断价值。与非肿瘤样本相比,OSCC中共鉴定出66个差异表达的lncRNA、80个miRNA和1149个mRNA。在根据新颖性筛选lncRNA,并预测lncRNA-miRNA和miRNA-mRNA相互作用后,发现了LINC00839/miR-195-5p/CCNE1轴。RT-qPCR显示LINC00839和CCNE1的上调伴随着miR-195-5p的下调。LINC00839与CCNE1 mRNA表达之间存在显著正相关,LINC00839与miR-195-5p表达之间存在显著负相关。此外,LINC00839的升高与肿瘤分级和淋巴结状态相关,而miR-195-5p的降低与淋巴、深度和血管侵犯相关(p < 0.05)。联合ROC曲线显示曲线下面积显著为0.93。这一发现揭示了OSCC肿瘤发生的一种新的调控机制,可能为治愈这种毁灭性癌症提供有效的诊断方法和潜在的治疗靶点。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d65/11686358/0bfe19330ee8/41598_2024_82922_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d65/11686358/903feeb1421a/41598_2024_82922_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d65/11686358/0519fef1957e/41598_2024_82922_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d65/11686358/9e3581636a9f/41598_2024_82922_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d65/11686358/a071498e6688/41598_2024_82922_Fig8_HTML.jpg
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