Multiple Signatures of the JC Polyomavirus in Paired Normal and Altered Colorectal Mucosa Indicate a Link with Human Colorectal Cancer, but Not with Cancer Progression

The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient's cohorts, and methods. Studies of...

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Published inInternational journal of molecular sciences Vol. 20; no. 23; p. 5965
Main Authors Uleri, Elena, Piu, Claudia, Caocci, Maurizio, Ibba, Gabriele, Sanges, Francesca, Pira, Giovanna, Murgia, Luciano, Barmina, Michele, Giannecchini, Simone, Porcu, Alberto, Serra, Caterina, Scanu, Antonio M, De Miglio, Maria R, Dolei, Antonina
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Abstract The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient's cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen ( ), Viral Protein 1 ( ), and in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp DNA rearrangement was detected. levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, expression decreased with CRC progression. expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.
AbstractList The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient's cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen ( ), Viral Protein 1 ( ), and in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp DNA rearrangement was detected. levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, expression decreased with CRC progression. expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.
The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient’s cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen (T-Ag), Viral Protein 1 (Vp1), and miR-J1-5p in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region (NCCR) DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp NCCR DNA rearrangement was detected. T-Ag levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, miR-J1-5p expression decreased with CRC progression. Vp1 expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.
The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient’s cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen ( T-Ag ), Viral Protein 1 ( Vp1 ), and miR-J1-5p in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region (NCCR) DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp NCCR DNA rearrangement was detected. T-Ag levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, miR-J1-5p expression decreased with CRC progression. Vp1 expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.
Author De Miglio, Maria R
Sanges, Francesca
Dolei, Antonina
Uleri, Elena
Piu, Claudia
Scanu, Antonio M
Giannecchini, Simone
Pira, Giovanna
Serra, Caterina
Ibba, Gabriele
Murgia, Luciano
Porcu, Alberto
Caocci, Maurizio
Barmina, Michele
AuthorAffiliation 3 Department of Experimental and Clinical Medicine, University of Florence, viable Morgagni 50, 50134 Florence, Italy; simone.giannecchini@unifi.it
1 Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy; elenauleri@tiscali.it (E.U.); claudia-piu@tiscali.it (C.P.); maurizio.caocci@yahoo.it (M.C.); G.ibba@gmx.com (G.I.); f.sanges@yahoo.it (F.S.); gpira@uniss.it (G.P.); cserra@uniss.it (C.S.)
2 Department of Experimental Surgery and Medical Sciences, University of Sassari, viable san Pietro 8, 07100 Sassari, Italy; lmurgia@uniss.it (L.M.); michelebarmina@gmail.com (M.B.); alberto@uniss.it (A.P.); scanu@uniss.it (A.M.S.); demiglio@uniss.it (M.R.D.M.)
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Keywords JC polyomavirus
adenomatous polyps
colorectal cancer
T-antigen
NCCR non-coding control region
oncogenesis
Language English
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Snippet The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and...
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StartPage 5965
SubjectTerms Adenocarcinoma
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adenocarcinoma - virology
Adenoma
Adenoma - metabolism
Adenoma - pathology
Adenoma - virology
Aged
Antigens
Antigens, Viral, Tumor - metabolism
Cell cycle
Chromosomes
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Colonic Neoplasms - virology
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Colorectal Neoplasms - virology
Deoxyribonucleic acid
Disease Progression
DNA
DNA, Viral - genetics
Female
Gene expression
Genomes
Humans
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
Intestinal Mucosa - virology
JC Virus - pathogenicity
Lesions
Male
Medical prognosis
Metastasis
MicroRNAs
Middle Aged
mRNA
Mucosa
Polymerase chain reaction
Polyomavirus Infections - metabolism
Polyomavirus Infections - pathology
Polyomavirus Infections - virology
Polyps
Proteins
Tumor Virus Infections - metabolism
Tumor Virus Infections - pathology
Tumor Virus Infections - virology
Tumorigenesis
Tumors
VP1 protein
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Title Multiple Signatures of the JC Polyomavirus in Paired Normal and Altered Colorectal Mucosa Indicate a Link with Human Colorectal Cancer, but Not with Cancer Progression
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Volume 20
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