Dysregulation of a Subset of Circulating and Vesicle-Associated miRNA in Pancreatic Cancer

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2024-05-01 DOI:10.3390/ncrna10030029

Giulia Girolimetti, Iulia Andreea Pelisenco, L. Eusebi, Claudio Ricci, Beatrice Cavina, Ivana Kurelac, T. Verri, Matteo Calcagnile, Pietro Alifano, Alessandro Salvi, Cecilia Bucci, Flora Guerra

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasia, characterized by early metastasis, low diagnostic rates at early stages, resistance to drugs, and poor prognosis. There is an urgent need to better characterize this disease in order to identify efficient diagnostic/prognostic biomarkers. Since microRNAs (miRNAs) contribute to oncogenesis and metastasis formation in PDAC, they are considered potential candidates for fulfilling this task. In this work, the levels of two miRNA subsets (involved in chemoresistance or with oncogenic/tumor suppressing functions) were investigated in a panel of PDAC cell lines and liquid biopsies of a small cohort of patients. We used RT-qPCR and droplet digital PCR (ddPCR) to measure the amounts of cellular- and vesicle-associated, and circulating miRNAs. We found that both PDAC cell lines, also after gemcitabine treatment, and patients showed low amounts of cellular-and vesicle-associated miR-155-5p, compared to controls. Interestingly, we did not find any differences when we analyzed circulating miR-155-5p. Furthermore, vesicle-related miR-27a-3p increased in cancer patients compared to the controls, while circulating let-7a-5p, miR-221-3p, miR-23b-3p and miR-193a-3p presented as dysregulated in patients compared to healthy individuals. Our results highlight the potential clinical significance of these analyzed miRNAs as non-invasive diagnostic molecular tools to characterize PDAC.

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胰腺癌中循环和囊泡相关 miRNA 亚群的调控失调

胰腺导管腺癌（PDAC）是侵袭性最强的肿瘤之一，其特点是转移早、早期诊断率低、耐药和预后差。目前迫切需要更好地描述这种疾病的特征，以确定有效的诊断/预后生物标志物。由于微小RNA（miRNA）在PDAC的肿瘤发生和转移形成中起着重要作用，因此被认为是完成这一任务的潜在候选者。在这项研究中，我们在一组 PDAC 细胞系和一小群患者的液体活检组织中调查了两种 miRNA 亚群（参与化疗抵抗或具有致癌/抑瘤功能）的水平。我们采用 RT-qPCR 和液滴数字 PCR (ddPCR) 技术测量了细胞、囊泡相关和循环 miRNA 的数量。我们发现，与对照组相比，同样经过吉西他滨治疗的 PDAC 细胞系和患者的细胞与囊泡相关 miR-155-5p 含量都很低。有趣的是，我们在分析循环 miR-155-5p 时没有发现任何差异。此外，与对照组相比，癌症患者与囊泡相关的 miR-27a-3p 增加了，而与健康人相比，患者循环中的 let-7a-5p、miR-221-3p、miR-23b-3p 和 miR-193a-3p 出现了失调。我们的研究结果凸显了这些被分析的 miRNAs 作为非侵入性诊断分子工具来描述 PDAC 特征的潜在临床意义。

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.

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