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IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2025-03-04 DOI:10.3390/ncrna11020022

Elena Golovina, Cory Eaton, Virginia Cox, Jozef Andel, Karina Savvulidi Vargova

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引用次数: 0

摘要

环状 RNA（circRNA）约占人类转录组的 10%。环状 RNA 属于非编码 RNA 的大类，其特点是通过反拼接形成稳定的环状回路。它们的主要作用是通过抑制 miRNA 的表达来调节转录，即 miRNA 海绵化。CircRNA 通过在 miRNA 结合位点与 miRNA 竞争性结合，促进肿瘤发生/淋巴瘤形成。在弥漫大 B 细胞淋巴瘤（DLBCL）中，已经发现了几种循环 RNA，它们的表达与肿瘤的进展和治疗反应有关。弥漫性大 B 细胞淋巴瘤是 B 细胞淋巴瘤中发病率最高、侵袭性最强的亚型，约占所有非霍奇金淋巴瘤的 25% 至 30%。DLBCL在组织病理学、生物学和遗传学方面表现出很大的异质性。经过一线治疗后复发或难治的患者预后很差，这表明对新治疗方案的需求尚未得到满足。随着未来更多的 circRNA 被鉴定出来，我们将更好地了解它们在治疗包括 DLBCL 在内的癌症中的生物学作用和潜在用途。例如，circAmotl1 可促进 MYC 的核转位和 MYC 转化靶点的上调，从而增强淋巴瘤的发生。另一个例子是 circAPC，它在 DLBCL 中明显下调，与疾病的侵袭性和不良预后相关。CircAPC会增加宿主基因腺瘤性息肉病大肠杆菌（APC）的表达，从而使典型的Wnt/β-catenin信号失活，抑制DLBCL的生长。MiRNA 属于非编码调控分子，它们通过其靶 mRNA 对淋巴瘤的发生起着重要作用。在DLBCL中，高表达的miRNA包括调控NF-ĸB和PI3K/AKT信号通路的miR-155-5p和miR-21-5p。本综述旨在描述 circRNAs 在 DLBCL 中调控 miRNAs 表达的功能和机制。这将有助于我们更好地理解 circRNA/miRNA/mRNA 的调控网络，并提出治疗 DLBCL 的新靶点。

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Mechanism of Action of circRNA/miRNA Network in DLBCL.

Circular RNAs (circRNAs) make up approximately 10% of the human transcriptome. CircRNAs belong to the broad group of non-coding RNAs and characteristically are formed by backsplicing into a stable circular loop. Their main role is to regulate transcription through the inhibition of miRNAs' expression, termed miRNA sponging. CircRNAs promote tumorigenesis/lymphomagenesis by competitively binding to miRNAs at miRNA binding sites. In diffuse large B-cell lymphoma (DLBCL), several circRNAs have been identified and their expression is related to both progression and response to therapy. DLBCL is the most prevalent and aggressive subtype of B-cell lymphomas and accounts for about 25% to 30% of all non-Hodgkin lymphomas. DLBCL displays great heterogeneity concerning histopathology, biology, and genetics. Patients who have relapsed or have refractory disease after first-line therapy have a very poor prognosis, demonstrating an important unmet need for new treatment options. As more circRNAs are identified in the future, we will better understand their biological roles and potential use in treating cancer, including DLBCL. For example, circAmotl1 promotes nuclear translocation of MYC and upregulation of translational targets of MYC, thus enhancing lymphomagenesis. Another example is circAPC, which is significantly downregulated in DLBCL and correlates with disease aggressiveness and poor prognosis. CircAPC increases expression of the host gene adenomatous polyposis coli (APC), and in doing so inactivates the canonical Wnt/β-catenin signaling and restrains DLBCL growth. MiRNAs belong to the non-coding regulatory molecules that significantly contribute to lymphomagenesis through their target mRNAs. In DLBCL, among the highly expressed miRNAs, are miR-155-5p and miR-21-5p, which regulate NF-ĸB and PI3K/AKT signaling pathways. The aim of this review is to describe the function and mechanism of regulation of circRNAs on miRNAs' expression in DLBCL. This will help us to better understand the regulatory network of circRNA/miRNA/mRNA, and to propose novel therapeutic targets to treat DLBCL.

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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.