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BCL2L1 受 lncRNA MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA 轴调控,可作为胰腺腺癌治疗和预后的生物标志物。

BCL2L1 is regulated by the lncRNA MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis and serves as a biomarker for pancreatic adenocarcinoma treatment and prognosis.

机构信息

Department of Neurosurgery, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, China.

Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, 210009, China.

出版信息

Gene. 2024 Oct 20;925:148615. doi: 10.1016/j.gene.2024.148615. Epub 2024 May 23.

DOI:10.1016/j.gene.2024.148615
PMID:38788819
Abstract

Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers. After escaping death, cancer cells are made more metastatic, aggressive, and also drug-resistant through anoikis resistance. The aim of this study is to explore the molecular mechanisms of anoikis-related genes in PAAD and to identify potential key biomarkers. We integrated information about PAAD from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases and identified anoikis-related gene BCL2L1 by survival analysis, univariate Cox regression analysis, and multifactorial Cox regression analysis. Various bioinformatics approaches showed that BCL2L1 was a valuable prognostic marker that might be involved in PAAD development and progression through different mechanisms, including cancer intervention, genomic heterogeneity, and RNA modifications. Our analysis showed that BCL2L1 expression also closely correlates with the expression of various immune checkpoint inhibitors. In particular, we found that long non-coding RNA MIR4435-2HG acted as ceRNA sponging miR-513a-5p to promote the expression of BCL2L1, thereby promoting pancreatic cancer cells proliferation. In conclusion, BCL2L1 expression regulated by the MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis might be used as a biomarker for cancer prognosis, treatment selection, and follow-up in PAAD patients.

摘要

胰腺导管腺癌 (PAAD) 是最恶性的癌症之一。癌细胞在逃避死亡后,通过抗失巢凋亡,变得更具转移性、侵袭性和耐药性。本研究旨在探讨与失巢凋亡相关的基因在 PAAD 中的分子机制,并鉴定潜在的关键生物标志物。我们整合了来自癌症基因组图谱 (TCGA) 和基因-组织表达 (GTEx) 数据库的 PAAD 信息,并通过生存分析、单因素 Cox 回归分析和多因素 Cox 回归分析鉴定出与失巢凋亡相关的基因 BCL2L1。各种生物信息学方法表明,BCL2L1 是一个有价值的预后标志物,可能通过不同的机制参与 PAAD 的发生和发展,包括癌症干预、基因组异质性和 RNA 修饰。我们的分析表明,BCL2L1 的表达也与各种免疫检查点抑制剂的表达密切相关。特别是,我们发现长非编码 RNA MIR4435-2HG 作为 ceRNA 海绵吸附 miR-513a-5p 来促进 BCL2L1 的表达,从而促进胰腺癌细胞增殖。总之,受 MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA 轴调控的 BCL2L1 表达可能作为 PAAD 患者癌症预后、治疗选择和随访的生物标志物。

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