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NBAT1/miR-21轴在结直肠癌进展中的作用及PVT-1基因多态性对miR-145表达水平的影响及其临床意义

NBAT1/miR-21 axis in progression of colorectal cancer and impact of PVT-1 polymorphism on miR-145 expression level and its clinical significance.

作者信息

Ayeldeen Ghada, Zaki Ahmed K, Amer Eman, Abdellatif Zeinab, Shaker Olfat G, Said Mohamed, Abdelhamid Amr M

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Department of Clinical and Chemical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Contemp Oncol (Pozn). 2024;28(4):304-317. doi: 10.5114/wo.2024.146961. Epub 2025 Jan 15.

Abstract

INTRODUCTION

Patients with colorectal cancer (CRC) have a higher chance of survival when the disease is detected and treated effectively at an early stage. Plasmacytoma variant translocation 1 (PVT-1), an oncogenic lncRNA, and neuroblastoma associated trans-cript 1 (NBAT1), a tumor suppressor lncRNA, have been linked to CRC progression, acting as competing endo-genous RNAs to the tumor suppressor miRNA-145 and oncomiRNA-21. The aim of the current study was to construct a competing endogenous RNA (ceRNA) associated with CRC. In addition, we aimed to investigate the impact of single nucleotide polymorphisms in the rs13255292 lncRNA PVT-1 on miR-145 expression levels and the lncRNA-NBAT1/miR-21 axis in the progression of CRC.

MATERIAL AND METHODS

Bioinforma-tic analysis was performed to determine differentially expressed genes (DEGs), differentially expressed micro-RNAs (DEMs), and differentially expressed lncRNAs (DELs) in CRC. PVT-1 rs13255292 C/T was genotyped and serum PVT-1, NBAT-1, miRNA-145 and miRNA-21 were assessed by qPCR in 85 CRC patients, 80 AP, and 85 controls.

RESULTS

The frequencies of the PVT-1 rs13255292 CT/TT genotype and T al-le-- le were significantly elevated in the CRC group compared to the controls. PVT-1 serum levels significantly increased due to the presence of the T allele in the studied groups, which was associated with downregulation of the miR-145 tumor suppressor. Also, the expression of NBAT-1 was significantly down-expressed, while that of oncomiR-21 was significantly elevated.

CONCLUSIONS

Bioinformatics analyses provides effective identification of potential lncRNAs linked with CRC. PVT-1/miR-145 and NBAT1/miR-21 are being investigated as potential non-invasive diagnostic biomarkers for CRC.

摘要

引言

结直肠癌(CRC)患者若在疾病早期得到有效检测和治疗,其生存几率更高。浆细胞瘤变异易位1(PVT-1)是一种致癌性长链非编码RNA,神经母细胞瘤相关转录本1(NBAT1)是一种肿瘤抑制性长链非编码RNA,它们与CRC进展相关,作为肿瘤抑制性微小RNA-145(miRNA-145)和致癌微小RNA-21(oncomiRNA-21)的竞争性内源性RNA发挥作用。本研究的目的是构建一个与CRC相关的竞争性内源性RNA(ceRNA)。此外,我们旨在研究lncRNA PVT-1中rs13255292单核苷酸多态性对miR-145表达水平以及CRC进展中lncRNA-NBAT1/miR-21轴的影响。

材料与方法

进行生物信息学分析以确定CRC中差异表达基因(DEG)、差异表达微小RNA(DEM)和差异表达长链非编码RNA(DEL)。对85例CRC患者、80例腺瘤性息肉(AP)患者和85例对照进行PVT-1 rs13255292 C/T基因分型,并通过qPCR评估血清PVT-1、NBAT-1、miRNA-145和miRNA-21。

结果

与对照组相比,CRC组中PVT-1 rs13255292 CT/TT基因型和T等位基因的频率显著升高。由于研究组中存在T等位基因,PVT-1血清水平显著升高,这与肿瘤抑制性miR-145的下调相关。此外,NBAT-1的表达显著下调,而致癌性miR-21的表达显著升高。

结论

生物信息学分析可有效鉴定与CRC相关的潜在长链非编码RNA。PVT-1/miR-145和NBAT1/miR-21正作为CRC潜在的非侵入性诊断生物标志物进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ab2/11809565/f032b5211886/WO-28-55533-g001.jpg

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