鉴定 RBM15 作为前列腺癌的预后生物标志物，涉及预后 m6A 相关 lncRNAs 的调控。

Identification of RBM15 as a prognostic biomarker in prostate cancer involving the regulation of prognostic m6A-related lncRNAs.

机构信息

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, Guangdong, China.

出版信息

Eur J Med Res. 2024 Aug 8;29(1):411. doi: 10.1186/s40001-024-02000-5.

DOI:10.1186/s40001-024-02000-5

PMID:39118157

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11312177/

Abstract

BACKGROUND

Long noncoding RNAs (lncRNAs) and N6-methyladenosine (m6A) modification of RNA play pivotal roles in tumorigenesis and cancer progression. However, knowledge regarding the expression patterns of m6A-related lncRNAs and their corresponding m6A regulators in prostate cancer (PCa) is limited. This study aimed to delineate the landscape of m6A-related lncRNAs, develop a predictive model, and identify the critical m6A regulators of prognostic lncRNAs in PCa.

METHODS

Clinical and transcriptome data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA) database. Prognostic m6A-related lncRNAs were subsequently identified through Pearson correlation and univariate Cox regression analyses. The prognostic lncRNAs were clustered into two groups by consensus clustering analysis, and a risk signature model was constructed using least absolute shrinkage and selection operator (LASSO) regression analysis of the lncRNAs. This model was evaluated using survival, clinicopathological, and immunological analyses. Furthermore, based on the constructed lncRNA-m6A regulatory network and RT-qPCR results, RBM15 was identified as a critical regulator of m6A-related lncRNAs. The biological roles of RBM15 in PCa were explored through bioinformatics analysis and biological experiments.

RESULTS

Thirty-four prognostic m6A-related lncRNAs were identified and categorized into two clusters with different expression patterns and survival outcomes in PCa patients. Seven m6A lncRNAs (AC105345.1, AL354989.1, AC138028.4, AC022211.1, AC020558.2, AC004076.2, and LINC02666) were selected to construct a risk signature with robust predictive ability for overall survival and were correlated with clinicopathological characteristics and the immune microenvironment of PCa patients. Among them, LINC02666 and AC022211.1 were regulated by RBM15. In addition, RBM15 expression correlated with PCa progression, survival, and the immune response. Patients with elevated RBM15 expression were more susceptible to the drug AMG-232. Moreover, silencing RBM15 decreased the viability of PCa cells and promoted apoptosis.

CONCLUSION

RBM15 is involved in the regulation of prognostic lncRNAs in the risk signature and has a robust predictive ability for PCa, making it a promising biomarker in PCa.

摘要

背景

长非编码 RNA（lncRNA）和 RNA 的 N6-甲基腺苷（m6A）修饰在肿瘤发生和癌症进展中起着关键作用。然而，关于前列腺癌（PCa）中 m6A 相关 lncRNA 的表达模式及其相应的 m6A 调节剂的知识有限。本研究旨在描绘 m6A 相关 lncRNA 的图谱，构建预测模型，并确定 PCa 中预后 lncRNA 的关键 m6A 调节剂。

方法

从癌症基因组图谱（TCGA）数据库中下载了 PCa 患者的临床和转录组数据。通过 Pearson 相关性和单因素 Cox 回归分析鉴定预后 m6A 相关 lncRNA。通过共识聚类分析将预后 lncRNA 聚类为两组，并使用最小绝对值收缩和选择算子（LASSO）回归分析构建 lncRNA 风险签名模型。通过生存、临床病理和免疫分析评估该模型。此外，基于构建的 lncRNA-m6A 调控网络和 RT-qPCR 结果，鉴定 RBM15 为 m6A 相关 lncRNA 的关键调控因子。通过生物信息学分析和生物学实验探索 RBM15 在 PCa 中的生物学作用。

结果

鉴定了 34 个预后 m6A 相关 lncRNA，并根据在 PCa 患者中的不同表达模式和生存结局将其分为两组。七个 m6A lncRNA（AC105345.1、AL354989.1、AC138028.4、AC022211.1、AC020558.2、AC004076.2 和 LINC02666）被选择用于构建具有稳健预测能力的总生存期风险签名，并与 PCa 患者的临床病理特征和免疫微环境相关。其中，LINC02666 和 AC022211.1 受 RBM15 调控。此外，RBM15 的表达与 PCa 进展、生存和免疫反应相关。RBM15 表达升高的患者更容易受到 AMG-232 药物的影响。此外，沉默 RBM15 降低了 PCa 细胞的活力并促进了细胞凋亡。