解码癌症:PVT1 内含子 10 与 MCM3 的同源性

IF 2.5 4区 医学 Q1 MEDICINE, GENERAL & INTERNAL Journal of the National Medical Association Pub Date : 2024-08-01 DOI:10.1016/j.jnma.2024.07.017
Eleonora Achrak BS
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引用次数: 0

摘要

目的 前列腺癌仍然是导致男性死亡的主要原因,部分原因是早期检测面临挑战。本研究调查了浆细胞瘤变异易位 1(PVT1)内含子 10,假设该内含子 10 在前列腺癌组织中过表达,并与 DNA 复制蛋白 MCM3 存在结构同源性,有可能打破内含子仅仅是非编码序列的观念。使用 TSVdb 对转录本的过表达进行量化,并通过 BLAST 与主要数据库进行比对,确定基因/结构同源性。HotSpot Wizard 评估三维结构同源性,而 SpliceRover 则检测剪接图案。通过比较 dbGaP 数据库中的表达水平,验证了临床相关性。结果发现 PVT1 内含子 10 存在显著的过表达,特定外显子和内含子的表达量增加了 4.3 倍。蛋白质组同源性分析表明,PVT1 与必需蛋白的相似度高达 85%,其中与 MCM3 的结构比对为 68.8%。三维结构比较也支持这些发现。结论 PVT1 内含子 10 在前列腺癌组织中的显著过表达以及与 MCM3 蛋白的结构相似性表明它具有潜在的功能性作用,打破了人们对内含子区域的传统认识。这些见解将内含子 10 定位为一种有前景的生物标记物和治疗靶点,通过对替代剪接和蛋白质同源性的深入了解,为前列腺癌的诊断和治疗提供了新的方向。
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Decoding Cancer: PVT1 Intron 10’s homology with MCM3

Purpose

Prostate cancer remains a leading cause of mortality among men, partly due to challenges in early detection. This study investigates Plasmacytoma Variant Translocation 1 (PVT1) intron 10, hypothesized to overexpress in prostate cancer tissues and exhibit structural homology with the DNA replication protein MCM3, potentially defying the notion of introns as mere non-coding sequences.

Methods

An analysis of 550 patient-derived prostate adenocarcinoma transcripts was conducted. Transcript overexpression was quantified using TSVdb, and genetic/structural homology was determined through BLAST against major databases. HotSpot Wizard assessed 3D structural homology, while SpliceRover detected splicing motifs. Clinical relevance was verified by comparing expression levels in the dbGaP database.

Results

Significant overexpression of PVT1 intron 10 was found, with a 4.3-fold increase noted in specific exons and introns. Proteomic homology analysis revealed an 85% similarity with essential proteins, including a 68.8% structural alignment with MCM3. The 3D structural comparisons supported these findings. Database validation confirmed a 5.3-fold overexpression of intron 10 in cancerous tissues.

Conclusion

PVT1 intron 10′s significant overexpression and structural similarity to MCM3 protein in prostate cancer tissue suggests a potential functional role, disrupting the conventional understanding of intronic regions. These insights position intron 10 as a promising biomarker and therapeutic target, offering new directions in prostate cancer diagnostics and treatment through a refined understanding of alternative splicing and protein homology.

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来源期刊
CiteScore
4.80
自引率
3.00%
发文量
139
审稿时长
98 days
期刊介绍: Journal of the National Medical Association, the official journal of the National Medical Association, is a peer-reviewed publication whose purpose is to address medical care disparities of persons of African descent. The Journal of the National Medical Association is focused on specialized clinical research activities related to the health problems of African Americans and other minority groups. Special emphasis is placed on the application of medical science to improve the healthcare of underserved populations both in the United States and abroad. The Journal has the following objectives: (1) to expand the base of original peer-reviewed literature and the quality of that research on the topic of minority health; (2) to provide greater dissemination of this research; (3) to offer appropriate and timely recognition of the significant contributions of physicians who serve these populations; and (4) to promote engagement by member and non-member physicians in the overall goals and objectives of the National Medical Association.
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