子宫内膜癌中的 MicroRNA 表达:现有知识和治疗意义。

MicroRNA Expression in Endometrial Cancer: Current Knowledge and Therapeutic Implications.

机构信息

Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Division of Medical Oncology, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

出版信息

Medicina (Kaunas). 2024 Mar 15;60(3):486. doi: 10.3390/medicina60030486.

Abstract

: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA molecules, each of which consists of 15-22 nucleotides and post-transcriptionally modulates gene expression. The complementary mRNAs-onto which the miRNAs hybridize-are involved in processes such as implantation, tumor suppression, proliferation, angiogenesis, and metastasis that define the entire tumor microenvironment. The endometrial biopsy is a standard technique used to recognize cellular atypia, but other non-invasive markers may reduce patient discomfort during the use of invasive methods. The present study aims to examine the distribution and the regulation of the differentially expressed miRNAs (DEMs) and EV-derived substances in women with endometrial cancer. : We systematically searched the PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect databases in April 2023, adopted the string "Endometrial Neoplasms AND Exosomes", and followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We selected all the studies that included patients with endometrial cancer and that described the regulation of miRNA molecules in that context. The differences in molecule expression between patients and controls were evaluated as significant when the proteins had a fold change of ±1.5. : Seventeen records fulfilled the inclusion criteria: a total of 371 patients and 273 controls were analyzed. The upregulated molecules that had the widest delta between endometrial cancer patients and controls-relative expression ≥ 1 > 3 log2(ratio)-were miR-20b-5p, miR-204-5p, miR-15a-5p, and miR-320a. In particular, miR-20b-5p and miR-204-5p were extracted from both serum and endometrial specimens, whereas miR-15a-5p was only isolated from plasma, and miR-320a was only extracted from the endometrial specimens. In parallel, the most downregulated miRNA in the endometrial cancer patients compared to the healthy subjects was miR-320a, which was found in the endometrial specimens. : Although their epigenetic regulation remains unknown, these upregulated molecules derived from EVs are feasible markers for the early detection of endometrial cancer. The modulation of these miRNA molecules should be assessed during different treatments or if recurrence develops in response to a targeted treatment modality.

摘要

细胞外囊泡是一类源自细胞的亚微米颗粒,通过 microRNA(miRNA)介导细胞间通讯。miRNA 是一组 RNA 分子,每个 miRNA 由 15-22 个核苷酸组成,通过转录后调控基因表达。miRNA 杂交的互补 mRNAs 参与到着床、肿瘤抑制、增殖、血管生成和转移等过程中,这些过程定义了整个肿瘤微环境。子宫内膜活检是一种用于识别细胞异型性的标准技术,但其他非侵入性标志物可能会减少患者在使用侵入性方法时的不适。本研究旨在检查子宫内膜癌患者中差异表达 miRNA(DEM)和 EV 衍生物质的分布和调节。我们于 2023 年 4 月系统地检索了 PubMed、EMBASE、Scopus、Cochrane Library 和 ScienceDirect 数据库,采用了“子宫内膜肿瘤 AND 外泌体”的检索词,并遵循了系统评价和荟萃分析的 Preferred Reporting Items(PRISMA)声明的建议。我们选择了所有包含子宫内膜癌患者并描述了该背景下 miRNA 分子调节的研究。当蛋白质的 fold change 为±1.5 时,患者和对照组之间分子表达的差异被评估为显著。符合纳入标准的记录有 17 条:共分析了 371 名患者和 273 名对照。与对照组相比,在子宫内膜癌患者中上调幅度最大(相对表达≥1 > 3 log2(ratio))的分子是 miR-20b-5p、miR-204-5p、miR-15a-5p 和 miR-320a。特别是 miR-20b-5p 和 miR-204-5p 既从血清中又从子宫内膜标本中提取,而 miR-15a-5p 仅从血浆中分离,miR-320a 仅从子宫内膜标本中提取。同时,与健康受试者相比,在子宫内膜癌患者中下调最明显的 miRNA 是 miR-320a,它存在于子宫内膜标本中。尽管它们的表观遗传调控尚不清楚,但这些源自 EV 的上调分子是早期检测子宫内膜癌的可行标志物。应在不同的治疗期间或在针对特定治疗模式出现复发时评估这些 miRNA 分子的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c0/10972089/1a64ebf2608a/medicina-60-00486-g001.jpg

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