LncRNAs PVT1, HULC, and HOTTIP: A promising biomarker trio for diffuse large B-cell lymphoma

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-02-28 DOI:10.1016/j.genrep.2025.102182

Milad Shahsavari , Sedigheh Arbabian , Farzaneh Hosseini , Mohamad Reza Razavi

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引用次数: 0

Abstract

Background

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) and is characterized by heterogeneity in morphology, genetics, and behavior. While the standard immunochemotherapy regimen, R-CHOP, can lead to sustained complete remission in most patients, those with relapses and poor prognoses require alternative R2-CHOP therapy.

Methods

Experimental and bioinformatic approaches explored the signaling pathways of three critical lncRNAs, PVT1, HULC, and HOTTIP, and their biological functions. The expression of these lncRNAs was quantitatively evaluated using real-time PCR in 100 patients before and after conventional treatment.

Results

PVT1, HULC, and HOTTIP expression were significantly elevated by 7.412 ± 2.497, 6.42 ± 3.32, and 4.09 ± 2.38 folds, respectively, compared to normal cases (p < 0.001). The expression levels were significantly higher in DLBCL patients aged >60 than those aged <60. A significant positive correlation was observed between HULC and HOTTIP expression. Post-treatment measurements showed a significant downregulation of PVT1 and HOTTIP (p < 0.001 and p = 0.032, respectively). Overexpression of lncRNA-miRNA interaction network analysis indicated deregulated targets, including hsa-miR-200a-3p, hsa-miR-372-3p, hsa-miR-186-5p, and others.

Conclusions

The long non-coding RNAs (lncRNAs) PVT1, HULC, and HOTTIP, which exhibited elevated expression levels in patients with diffuse large B-cell lymphoma (DLBCL) before treatment and decreased to normal levels following treatment, could serve as valuable diagnostic biomarkers or prognostic indicators of treatment response. Their distinct conditional expression patterns across different age demographics further support their potential utility.

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LncRNAs PVT1， HULC和HOTTIP：弥漫性大b细胞淋巴瘤的一个有前途的生物标志物三人组

弥漫性大b细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤（NHL）亚型，其特点是在形态学、遗传学和行为上具有异质性。虽然标准的免疫化疗方案R-CHOP可以导致大多数患者持续完全缓解，但那些复发和预后不良的患者需要替代的R2-CHOP治疗。方法采用实验和生物信息学方法，探讨PVT1、HULC和HOTTIP三种关键lncrna的信号通路及其生物学功能。采用实时荧光定量PCR技术对100例患者在常规治疗前后的lncrna表达进行定量评价。结果spvt1、HULC、HOTTIP表达量较正常组分别提高7.412±2.497倍、6.42±3.32倍、4.09±2.38倍(p <；0.001)。60岁的DLBCL患者表达水平明显高于60岁的患者。HULC与HOTTIP表达呈显著正相关。治疗后测量显示PVT1和HOTTIP显著下调(p <；0.001和p = 0.032)。lncRNA-miRNA相互作用网络分析表明，调控靶点解除，包括hsa-miR-200a-3p、hsa-miR-372-3p、hsa-miR-186-5p等。结论长链非编码rna (lncRNAs) PVT1、HULC和HOTTIP在弥漫性大b细胞淋巴瘤（DLBCL）患者治疗前表达水平升高，治疗后表达水平降至正常水平，可作为有价值的诊断性生物标志物或预后指标。它们在不同年龄人口统计中的独特条件表达模式进一步支持了它们的潜在效用。

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

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.