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簇集素转录变体在甲状腺肿瘤中的表达：一种潜在的恶性肿瘤标志物？

Clusterin transcript variants expression in thyroid tumor: a potential marker of malignancy?

作者信息

Fuzio Paolo, Napoli Anna, Ciampolillo Anna, Lattarulo Serafina, Pezzolla Angela, Nuzziello Nicoletta, Liuni Sabino, Giorgino Francesco, Maiorano Eugenio, Perlino Elda

机构信息

Institute of Biomedical Technologies, National Research Council (CNR), Via G. Amendola, 122/D, 70126, Bari, Italy.

Department of Emergency and Organ Transplantation, Section of Pathological Anatomy, University of Bari Aldo Moro, 70124, Bari, Italy.

出版信息

BMC Cancer. 2015 May 2;15:349. doi: 10.1186/s12885-015-1348-0.

DOI:10.1186/s12885-015-1348-0
PMID:25934174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4422431/
Abstract

BACKGROUND

Clusterin (CLU) is a ubiquitous multifunctional factor involved in neoplastic transformation. The CLU transcript variants and protein forms play a crucial role in balancing cells proliferation and death.

METHODS

We investigated the regulation of CLU transcript variants expression in an in vivo model system consisting of both neoplastic tissues and fine needle aspiration biopsy (FNAB) samples isolated from patients undergoing thyroidectomy.

RESULTS

The immunohistochemical analyses showed an overall CLU up-regulation in papillary carcinoma. A specific CLU2 transcript variant increase was registered using qPCR in papillary carcinomas while CLU1 decreased. In addition, the analysis of CLU transcripts expression level showed an increase of the CLU2 transcript in the TIR 3 patients with histologically confirmed thyroid cancer.

CONCLUSIONS

Our results suggest the existence of a specific alteration of CLU2:CLU1 ratio towards CLU2, thus providing the first circumstantial evidence for the potential use of CLU transcript variants as effective biomarkers for a more accurate assessment of the so called "indeterminate" thyroid nodules.

摘要

背景

簇集素（CLU）是一种广泛存在的多功能因子，参与肿瘤转化过程。CLU转录变体和蛋白质形式在平衡细胞增殖和死亡中起关键作用。

方法

我们在一个体内模型系统中研究了CLU转录变体表达的调控，该系统由肿瘤组织和从接受甲状腺切除术的患者中分离的细针穿刺活检（FNAB）样本组成。

结果

免疫组织化学分析显示，乳头状癌中CLU总体上调。使用qPCR检测发现，乳头状癌中特定的CLU2转录变体增加，而CLU1减少。此外，对CLU转录本表达水平的分析表明，在组织学确诊为甲状腺癌的TIR 3患者中，CLU2转录本增加。

结论

我们的结果表明存在CLU2:CLU1比例向CLU2的特定改变，从而为将CLU转录变体作为有效的生物标志物用于更准确评估所谓的“不确定”甲状腺结节提供了首个间接证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/4d88126a44d2/12885_2015_1348_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/e194ad77d747/12885_2015_1348_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/6f22e1f096bf/12885_2015_1348_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/9ec7071e2b6c/12885_2015_1348_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/4d88126a44d2/12885_2015_1348_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/e194ad77d747/12885_2015_1348_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/6f22e1f096bf/12885_2015_1348_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/9ec7071e2b6c/12885_2015_1348_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71d3/4422431/4d88126a44d2/12885_2015_1348_Fig4_HTML.jpg

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Non-secreted clusterin isoforms are translated in rare amounts from distinct human mRNA variants and do not affect Bax-mediated apoptosis or the NF-κB signaling pathway.非分泌型簇集蛋白同工型是从不同的人 mRNA 变体中以少量翻译的，并不影响 Bax 介导的细胞凋亡或 NF-κB 信号通路。
PLoS One. 2013 Sep 20;8(9):e75303. doi: 10.1371/journal.pone.0075303. eCollection 2013.
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Regulation of the expression of CLU isoforms in endometrial proliferative diseases.
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PLoS One. 2021 Nov 12;16(11):e0259534. doi: 10.1371/journal.pone.0259534. eCollection 2021.
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Comprehensive Identification of Potential Crucial Genes and miRNA-mRNA Regulatory Networks in Papillary Thyroid Cancer.全面鉴定甲状腺乳头状癌中的潜在关键基因和 miRNA-mRNA 调控网络。
Biomed Res Int. 2021 Jan 12;2021:6752141. doi: 10.1155/2021/6752141. eCollection 2021.
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