Plasma miR-122-5p and miR-142-5p and their role in chemoresistance of colon cancer patients

IF 2.5 4区医学 Q3 GENETICS & HEREDITY

Mutagenesis Pub Date : 2024-09-14 DOI:10.1093/mutage/geae023

Klara Vokacova, Aneta Landecka, Saba Selvi, Josef Horak, Vendula Novosadova, Katerina Manakova, Miroslav Levy, Veronika Vymetalkova

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引用次数: 0

Abstract

Chemoresistance represents a major issue affecting cancer therapy efficacy. Because microRNAs (miRNAs) regulate gene expression on multiple levels, their role in chemoresistance development is reasonably certain. In our previous study, miR-122-5p and miR-142-5p were identified as diagnostic, prognostic, and predictive biomarkers for primary and metastatic rectal cancer. The aim of the present study was to investigate whether these miRNAs can also reflect the disease course of colon cancer (CC) patients. Further, we focused on a deeper understanding of their involvement in 5-fluorouracil (5-FU) chemoresistance development. The expression analysis of both miRNAs was analysed in repeated whole plasma samplings (n=3, approximately every 6 months) of CC patients (n=49) by RT-qPCR. Expression levels of both miRNAs were determined in the 5-FU sensitive and resistant CC cell lines. From RNA-seq profiles of both sensitive and 5-FU resistant DLD-1 cell lines, the expression levels of miR-122-5p and miR-142-5p validated target genes were detected and compared. Significant differences in the expression levels of both miRNAs between T0 and T1 or T2 samplings were observed. Further, an association between the occurrence of relapse and miR-122-5p expression levels was noticed. Patients who did not relapse had higher expression of miR-122-5p at T1 (p=0.01; 3.16-fold change) and T2 (p=0.04; 2.79-fold change) samplings in comparison with T0 sampling. Out of all miR-122-5p validated targets (n=102), 25 genes were significantly differentially expressed between sensitive and 5-FU-resistant cell lines. Our data suggest that miR-122-5p may represent a predictive marker of tumour relapse in CC patients. In vitro data suggests that this aspect may be linked to the potential therapeutic targets of miR-122-5p related to 5-FU-based chemoresistance. However, deeper mechanistic studies are still needed for progress toward personalized medicine.

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血浆 miR-122-5p 和 miR-142-5p 及其在结肠癌患者化疗耐药性中的作用

化疗耐药性是影响癌症疗效的一个主要问题。由于微RNA（miRNA）在多个水平上调控基因表达，因此它们在化疗耐药性发展中的作用是相当确定的。在我们之前的研究中，miR-122-5p 和 miR-142-5p 被确定为原发性和转移性直肠癌的诊断、预后和预测生物标志物。本研究旨在探讨这些 miRNA 是否也能反映结肠癌（CC）患者的病程。此外，我们还重点深入了解了这些miRNA参与5-氟尿嘧啶（5-FU）化疗耐药性发展的情况。我们利用 RT-qPCR 技术，在反复采集的 CC 患者（49 人）全血浆样本（3 份，约每 6 个月）中分析了这两种 miRNA 的表达情况。此外，还测定了 5-FU 敏感和耐药 CC 细胞系中这两种 miRNA 的表达水平。从敏感和耐受 5-FU 的 DLD-1 细胞系的 RNA-seq 图谱中，检测并比较了 miR-122-5p 和 miR-142-5p 验证靶基因的表达水平。在 T0 和 T1 或 T2 采样之间，观察到这两种 miRNA 的表达水平存在显著差异。此外，研究还发现复发与 miR-122-5p 的表达水平有关。与 T0 取样相比，未复发患者在 T1（p=0.01；变化 3.16 倍）和 T2（p=0.04；变化 2.79 倍）取样时的 miR-122-5p 表达水平较高。在所有经 miR-122-5p 验证的靶点（n=102）中，25 个基因在敏感细胞株和 5-FU 抗性细胞株之间有显著的表达差异。我们的数据表明，miR-122-5p 可能是 CC 患者肿瘤复发的预测标志物。体外数据表明，这一方面可能与 miR-122-5p 与 5-FU 化疗耐药性相关的潜在治疗靶点有关。不过，要想在个性化医疗方面取得进展，还需要进行更深入的机理研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutagenesis 生物-毒理学

CiteScore

5.90

自引率

3.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.