Possible Involvement of Long Non-Coding RNAs GNAS-AS1 and MIR205HG in the Modulation of 5-Fluorouracil Chemosensitivity in Colon Cancer Cells through Increased Extracellular Release of Exosomes.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2024-04-15 DOI:10.3390/ncrna10020025

S. Azwar, C. T. Ng, S. Y. Zahari Sham, H. F. Seow, Minhian Chai, Mohd Faizal Ghazali, M. F. Jabar

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Abstract

A growing number of studies have suggested the involvement of long non-coding RNAs as the key players in not just the initiation and progression of the tumor microenvironment, but also in chemotherapy tolerance. In the present study, generated 5-FU-resistant SW480/DR cells were analyzed via cDNA microarray for its aberrant lncRNAs and mRNAs expression in comparison with the 5-FU-susceptible SW480/DS cells. Among the 126 lncRNAs described, lncRNAs GNAS-AS1, MIR205HG, and LOC102723721 have been identified to be significantly upregulated, while lncRNs lnc-RP11-597K23.2.1-2, LOC100507639, and CCDC144NL-AS1 have been found to be significantly downregulated. In the meantime, bioinformatic analysis through gene ontology studies of aberrantly expressed mRNAs revealed "regulated exocytosis", among others, as the biological process most impacted in SW480/DR cells. To investigate, exosome purification was then carried out and its characterization were validated via transmission electron microscopy and nanoparticle tracking analysis. Interestingly, it was determined that the 5-FU-resistant SW480/DR cells secretes significantly higher concentration of extracellular vesicles, particularly, exosomes when compared to the 5-FU-susceptible SW480/DS cells. Based on the lncRNA-mRNA interaction network analysis generated, lncRNA GNAS-AS1 and MIR205HG have been identified to be potentially involved in the incidence of 5-FU resistance in SW480 colon cancer cells through promoting increased release of exosomes into the intercellular matrix. Our study hopes not only to provide insights on the list of involved candidate lncRNAs, but also to elucidate the role exosomes play in the initiation and development of 5-FU chemotherapy resistance in colon cancer cells.

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长非编码 RNA GNAS-AS1 和 MIR205HG 可能通过增加细胞外释放外泌体参与调节结肠癌细胞对 5 氟尿嘧啶的化疗敏感性

越来越多的研究表明，长非编码RNA不仅是肿瘤微环境发生和发展的关键因素，也是化疗耐受性的关键因素。本研究通过 cDNA 微阵列分析了生成的 5-FU 耐药 SW480/DR 细胞与 5-FU 易感 SW480/DS 细胞的异常 lncRNAs 和 mRNAs 表达。在所描述的126个lncRNA中，发现lncRNA GNAS-AS1、MIR205HG和LOC102723721被显著上调，而lncRN lnc-RP11-597K23.2.1-2、LOC100507639和CCDC144NL-AS1被显著下调。与此同时，通过对异常表达的 mRNA 进行基因本体论研究进行生物信息学分析，发现 "调控外泌 "等是在 SW480/DR 细胞中受影响最大的生物过程。研究人员随后进行了外泌体纯化，并通过透射电子显微镜和纳米粒子追踪分析验证了其特征。有趣的是，与对5-FU敏感的SW480/DS细胞相比，对5-FU耐药的SW480/DR细胞分泌的胞外囊泡浓度明显更高，尤其是外泌体。根据所生成的lncRNA-mRNA相互作用网络分析，发现lncRNA GNAS-AS1和MIR205HG可能通过促进外泌体向细胞间质的释放而参与了SW480结肠癌细胞5-FU耐药性的发生。我们的研究不仅希望提供有关候选lncRNA的见解，还希望阐明外泌体在结肠癌细胞5-FU化疗耐药性的产生和发展过程中所起的作用。

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

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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