研究长链非编码RNA 00092在乳腺癌患者中的潜在临床意义。

Investigating the potential clinical significance of long non-coding RNA 00092 in patients with breast cancer.

作者信息

Li Jingquan, Lu Fanghao, Shao Xin, You Bosen

机构信息

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

Department of Pathophysiology, Harbin Medical University, Harbin, China.

出版信息

Ann Transl Med. 2022 May;10(10):602. doi: 10.21037/atm-22-1956.

DOI:10.21037/atm-22-1956

PMID:35722403

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9201173/

Abstract

BACKGROUND

Aberrant promoter methylation and its resultant aberrant gene expression are important epigenetic mechanisms that promote the development of breast cancer (BC). However, the prognostic value of this type of methylation-driven gene in BC is unknown.

METHODS

To identify DNA methylation-driven long non-coding RNAs (lncRNAs), a comprehensive analysis of RNA-sequencing and DNA methylation data of 1,200 clinical samples was performed. Differentially expressed lncRNAs (DELs) and survival-related lncRNAs in BC were identified using the R package. The function of the lncRNA was evaluated using Kaplan-Meier and receiver operating characteristic (ROC) curve analyses. The expression of the key lncRNA in tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Biological functions of the key lncRNA were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The Connectivity Map (CMap) was used to search for small-molecule targeted drugs for the key lncRNA. The functions of the key lncRNA in BC progression were investigated using cell proliferation and cell cycle assays.

RESULTS

A total of 14 methylation-driven lncRNAs, 526 DELs, and 93 survival-associated lncRNAs were identified. The above data were intersected, and a unique lncRNA, , was obtained. was hypermethylated and hypoexpressed in both BC tissues and cell lines. was found to be a diagnostic marker for BC, with its low expression being associated with poor prognosis (P=0.013). overexpression inhibited the proliferation and cell cycle of BC cells . Nimesulide and sulpiride were screened out as potential targeted therapeutic drugs for in BC, and sulpiride was observed to partially reverse the proliferative effect of (small interfer) si- on BC cells.

CONCLUSIONS

is a methylation-driven lncRNA in BC and could be a potential therapeutic target for this disease.

摘要

背景

异常的启动子甲基化及其导致的异常基因表达是促进乳腺癌（BC）发生发展的重要表观遗传机制。然而，这种甲基化驱动基因在BC中的预后价值尚不清楚。

方法

为了鉴定DNA甲基化驱动的长链非编码RNA（lncRNA），对1200份临床样本的RNA测序和DNA甲基化数据进行了综合分析。使用R包鉴定BC中差异表达的lncRNA（DEL）和生存相关lncRNA。使用Kaplan-Meier和受试者工作特征（ROC）曲线分析评估lncRNA的功能。通过定量实时聚合酶链反应（qRT-PCR）检测关键lncRNA在组织和细胞中的表达。使用基因本体论和京都基因与基因组百科全书分析来分析关键lncRNA的生物学功能。使用连接图谱（CMap）搜索针对关键lncRNA的小分子靶向药物。使用细胞增殖和细胞周期测定法研究关键lncRNA在BC进展中的功能。

结果

共鉴定出14个甲基化驱动的lncRNA、526个DEL和93个生存相关lncRNA。对上述数据进行交集分析，得到一个独特的lncRNA，即。在BC组织和细胞系中均发生高甲基化且低表达。被发现是BC的诊断标志物，其低表达与不良预后相关（P = 0.013）。的过表达抑制了BC细胞的增殖和细胞周期。筛选出尼美舒利和舒必利作为BC中针对的潜在靶向治疗药物，并且观察到舒必利可部分逆转（小干扰）si- 对BC细胞的增殖作用。