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 in | International journal of molecular sciences Vol. 20; no. 23; p. 5965 |
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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. |
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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.) |
AuthorAffiliation_xml | – name: 3 Department of Experimental and Clinical Medicine, University of Florence, viable Morgagni 50, 50134 Florence, Italy; simone.giannecchini@unifi.it – name: 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.) – name: 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.) |
Author_xml | – sequence: 1 givenname: Elena orcidid: 0000-0003-1014-0042 surname: Uleri fullname: Uleri, Elena organization: Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy – sequence: 2 givenname: Claudia orcidid: 0000-0002-6601-1568 surname: Piu fullname: Piu, Claudia organization: Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy – sequence: 3 givenname: Maurizio surname: Caocci fullname: Caocci, Maurizio organization: Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy – sequence: 4 givenname: Gabriele surname: Ibba fullname: Ibba, Gabriele organization: Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy – sequence: 5 givenname: Francesca surname: Sanges fullname: Sanges, Francesca organization: Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy – sequence: 6 givenname: Giovanna surname: Pira fullname: Pira, Giovanna organization: Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy – sequence: 7 givenname: Luciano surname: Murgia fullname: Murgia, Luciano organization: Department of Experimental Surgery and Medical Sciences, University of Sassari, viable san Pietro 8, 07100 Sassari, Italy – sequence: 8 givenname: Michele surname: Barmina fullname: Barmina, Michele organization: Department of Experimental Surgery and Medical Sciences, University of Sassari, viable san Pietro 8, 07100 Sassari, Italy – sequence: 9 givenname: Simone orcidid: 0000-0003-3374-7621 surname: Giannecchini fullname: Giannecchini, Simone organization: Department of Experimental and Clinical Medicine, University of Florence, viable Morgagni 50, 50134 Florence, Italy – sequence: 10 givenname: Alberto surname: Porcu fullname: Porcu, Alberto organization: Department of Experimental Surgery and Medical Sciences, University of Sassari, viable san Pietro 8, 07100 Sassari, Italy – sequence: 11 givenname: Caterina orcidid: 0000-0002-4117-2234 surname: Serra fullname: Serra, Caterina organization: Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy – sequence: 12 givenname: Antonio M orcidid: 0000-0001-7878-1167 surname: Scanu fullname: Scanu, Antonio M organization: Department of Experimental Surgery and Medical Sciences, University of Sassari, viable san Pietro 8, 07100 Sassari, Italy – sequence: 13 givenname: Maria R surname: De Miglio fullname: De Miglio, Maria R organization: Department of Experimental Surgery and Medical Sciences, University of Sassari, viable san Pietro 8, 07100 Sassari, Italy – sequence: 14 givenname: Antonina orcidid: 0000-0001-5815-5310 surname: Dolei fullname: Dolei, Antonina organization: Department of Biomedical Sciences, University of Sassari, viale san Pietro 43B, 07100 Sassari, Italy |
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Keywords | JC polyomavirus adenomatous polyps colorectal cancer T-antigen NCCR non-coding control region oncogenesis |
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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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