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Tytuł pozycji:

Telomere-associated genes and telomeric lncRNAs are biomarker candidates in lung squamous cell carcinoma (LUSC).

Tytuł:
Telomere-associated genes and telomeric lncRNAs are biomarker candidates in lung squamous cell carcinoma (LUSC).
Autorzy:
Storti CB; Genetics Dept., Biosciences Institute, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
de Oliveira RA; Biostatistics Dept. Biosciences Institute, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
de Carvalho M; Faculty of Veterinary Medicine and Animal Science, Faculty of Medicine, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
Hasimoto EN; Department of Surgery and Orthopedics, Faculty of Medicine, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
Cataneo DC; Department of Surgery and Orthopedics, Faculty of Medicine, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
Cataneo AJM; Department of Surgery and Orthopedics, Faculty of Medicine, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
De Faveri J; Department of Pathology, Faculty of Medicine, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
Vasconcelos EJR; Leeds Omics, University of Leeds, United Kingdom.
Dos Reis PP; Department of Surgery and Orthopedics, Faculty of Medicine, Sao Paulo State University (UNESP), Botucatu, SP, Brazil; Experimental Research Unity (UNIPEX), Faculty of Medicine, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
Cano MIN; Genetics Dept., Biosciences Institute, Sao Paulo State University (UNESP), Botucatu, SP, Brazil. Electronic address: .
Źródło:
Experimental and molecular pathology [Exp Mol Pathol] 2020 Feb; Vol. 112, pp. 104354. Date of Electronic Publication: 2019 Dec 16.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: <2000- > : Amsteram : Elsevier
Original Publication: New York : Academic Press
MeSH Terms:
Adenocarcinoma/*genetics
Carcinoma, Non-Small-Cell Lung/*genetics
Neoplasms, Squamous Cell/*genetics
Telomere/*genetics
Adenocarcinoma/classification ; Adenocarcinoma/pathology ; Biomarkers, Tumor/genetics ; Brazil ; Carcinoma, Non-Small-Cell Lung/classification ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Cycle Proteins/genetics ; Cell Proliferation/genetics ; DNA-Binding Proteins/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Neoplasms, Squamous Cell/classification ; Neoplasms, Squamous Cell/pathology ; Nuclear Proteins/genetics ; RNA/genetics ; RNA, Long Noncoding/genetics ; Shelterin Complex ; Telomerase/genetics ; Telomere-Binding Proteins/genetics ; Transcription Factors/genetics ; Transcriptome/genetics
Contributed Indexing:
Keywords: LUAD; LUSC; Molecular biomarkers; Non-small cell lung cancer; Telomere-associated genes; Telomeres; Telomeric ncRNAs
Substance Nomenclature:
0 (Biomarkers, Tumor)
0 (Cell Cycle Proteins)
0 (DKC1 protein, human)
0 (DMRT2 protein, human)
0 (DNA-Binding Proteins)
0 (Nuclear Proteins)
0 (POT1 protein, human)
0 (RNA, Long Noncoding)
0 (Shelterin Complex)
0 (Telomere-Binding Proteins)
0 (Transcription Factors)
0 (telomerase RNA)
63231-63-0 (RNA)
EC 2.7.7.49 (TERT protein, human)
EC 2.7.7.49 (Telomerase)
Entry Date(s):
Date Created: 20191215 Date Completed: 20200715 Latest Revision: 20211204
Update Code:
20240105
DOI:
10.1016/j.yexmp.2019.104354
PMID:
31837325
Czasopismo naukowe
In the past decade, research efforts were made to identify molecular biomarkers useful as therapeutic targets in Non-Small Cell Lung Cancer (NSCLC), the most frequent type of lung carcinoma. NSCLC presents different histological subtypes being the most prevalent LUSC (Lung Squamous Cell Cancer) and LUAD (Lung Adenocarcinoma), and only a subset of LUAD patients' present tumors expressing known targetable genetic alterations. Telomeres and its components, including telomerase, the enzyme that replenishes telomeres, have been considered potential cancer biomarkers due to their crucial role in cell proliferation and genome stability. Our study aims to quantify expression changes affecting telomere-associated genes and ncRNAs associated with telomere regulation and maintenance in NSCLC. We first assessed the transcriptome (RNA-Seq) data of NSCLC patients from The Cancer Genome Atlas (TCGA) and then we tested the expression of telomere-associated genes and telomeric ncRNAs (TERC, telomerase RNA component, and TERRA, telomere repeat-containing RNA) in Brazilian NCSLC patient samples by quantitative RT-PCR, using matched normal adjacent tissue samples as the control. We also estimated the mean size of terminal restriction fragments (TRF) of some Brazilian NSCLC patients using telomeric Southern blot. The TCGA analysis identified alterations in the expression profile of TERT and telomere damage repair genes, mainly in the LUSC subtype. The study of Brazilian NSCLC samples by RT-qPCR showed that LUSC and LUAD express high amounts of TERT and that although the mean TRF size of tumor samples was shorter compared to normal cells, telomeres in NSCLC are probably maintained by telomerase. Also, the expression analysis of Brazilian NSCLC samples identified statistically significant alterations in the expression of genes involved with telomere damage repair, as well as in TERC and TERRA, mainly in the LUSC subtype. We, therefore, concluded that telomere maintenance genes are significantly deregulated in NSCLC, representing potential biomarkers in the LUSC subtype.
(Copyright © 2019 Elsevier Inc. All rights reserved.)

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