MicroRNA miR-J1-5p as a potential biomarker for JC virus infection in the gastrointestinal tract

Alexander Link, Francesc Balaguer, Takeshi Nagasaka, C. Richard Boland, Ajay Goel

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Introduction: JC virus (JCV), a human polyomavirus that causes progressive multifocal leukoencephalopathy (PML), has been linked to colorectal cancer (CRC). However, determination of JCV infection and its role in carcinogenesis has been challenging, highlighting the need for better diagnostic strategies for this virus. JCV-specific microRNAs (miRNAs) were identified and shown to negatively regulate oncogenic JCV T-Ag. Herein, we determined the pattern of JCV miRNA expression in clinical specimens from healthy subjects and CRC patients. Material and Methods: JCV miRNA expression was validated in CRC cell lines transfected with the JCV T-Ag. Results were confirmed using CRC tissues that were expressed T-Ag. Expression of JCV-specific miR-J1-5p was measured in fresh stool samples from healthy volunteers, and samples from fecal occult blood test kits from healthy subject, and patients with colorectal neoplasms. Results: JCV miR-J1-5p was detected in JCV-transfected, but not vector-transfected, CRC cells, and was stable between cell passages. MiR-J1-5p was present in all six JCV T-Ag+ CRC samples. Surprisingly, JCV miRNA was detectable in all normal tissues, but the expression was much lower in CRC tissues. Similarly, miR-J1-5p expression was present in all fecal samples, but expression was lower in CRCs compared to controls or adenoma patients. Conclusion: JC virus-specific miR-J1-5p miRNA is a potential biomarker for viral infection, and the lower expression in patients with colonic neoplasia highlights its biological role regulating oncogenic T-Ag expression in CRC. Impact: JCV-specific miRNA is a candidate for the development of a non-invasive screening test, as well as therapeutic intervention for JCV-associated diseases.

Original languageEnglish
Article numbere100036
JournalPLoS One
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 16 2014

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JC polyomavirus
JC Virus
Biomarkers
Virus Diseases
MicroRNAs
microRNA
Viruses
gastrointestinal system
Gastrointestinal Tract
biomarkers
colorectal neoplasms
Colorectal Neoplasms
infection
Healthy Volunteers
Tissue
Oncogenic viruses
Polyomavirus
Progressive Multifocal Leukoencephalopathy
sampling
Occult Blood

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

MicroRNA miR-J1-5p as a potential biomarker for JC virus infection in the gastrointestinal tract. / Link, Alexander; Balaguer, Francesc; Nagasaka, Takeshi; Boland, C. Richard; Goel, Ajay.

In: PLoS One, Vol. 9, No. 6, e100036, 16.06.2014.

Research output: Contribution to journalArticle

Link, Alexander ; Balaguer, Francesc ; Nagasaka, Takeshi ; Boland, C. Richard ; Goel, Ajay. / MicroRNA miR-J1-5p as a potential biomarker for JC virus infection in the gastrointestinal tract. In: PLoS One. 2014 ; Vol. 9, No. 6.
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abstract = "Introduction: JC virus (JCV), a human polyomavirus that causes progressive multifocal leukoencephalopathy (PML), has been linked to colorectal cancer (CRC). However, determination of JCV infection and its role in carcinogenesis has been challenging, highlighting the need for better diagnostic strategies for this virus. JCV-specific microRNAs (miRNAs) were identified and shown to negatively regulate oncogenic JCV T-Ag. Herein, we determined the pattern of JCV miRNA expression in clinical specimens from healthy subjects and CRC patients. Material and Methods: JCV miRNA expression was validated in CRC cell lines transfected with the JCV T-Ag. Results were confirmed using CRC tissues that were expressed T-Ag. Expression of JCV-specific miR-J1-5p was measured in fresh stool samples from healthy volunteers, and samples from fecal occult blood test kits from healthy subject, and patients with colorectal neoplasms. Results: JCV miR-J1-5p was detected in JCV-transfected, but not vector-transfected, CRC cells, and was stable between cell passages. MiR-J1-5p was present in all six JCV T-Ag+ CRC samples. Surprisingly, JCV miRNA was detectable in all normal tissues, but the expression was much lower in CRC tissues. Similarly, miR-J1-5p expression was present in all fecal samples, but expression was lower in CRCs compared to controls or adenoma patients. Conclusion: JC virus-specific miR-J1-5p miRNA is a potential biomarker for viral infection, and the lower expression in patients with colonic neoplasia highlights its biological role regulating oncogenic T-Ag expression in CRC. Impact: JCV-specific miRNA is a candidate for the development of a non-invasive screening test, as well as therapeutic intervention for JCV-associated diseases.",
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AB - Introduction: JC virus (JCV), a human polyomavirus that causes progressive multifocal leukoencephalopathy (PML), has been linked to colorectal cancer (CRC). However, determination of JCV infection and its role in carcinogenesis has been challenging, highlighting the need for better diagnostic strategies for this virus. JCV-specific microRNAs (miRNAs) were identified and shown to negatively regulate oncogenic JCV T-Ag. Herein, we determined the pattern of JCV miRNA expression in clinical specimens from healthy subjects and CRC patients. Material and Methods: JCV miRNA expression was validated in CRC cell lines transfected with the JCV T-Ag. Results were confirmed using CRC tissues that were expressed T-Ag. Expression of JCV-specific miR-J1-5p was measured in fresh stool samples from healthy volunteers, and samples from fecal occult blood test kits from healthy subject, and patients with colorectal neoplasms. Results: JCV miR-J1-5p was detected in JCV-transfected, but not vector-transfected, CRC cells, and was stable between cell passages. MiR-J1-5p was present in all six JCV T-Ag+ CRC samples. Surprisingly, JCV miRNA was detectable in all normal tissues, but the expression was much lower in CRC tissues. Similarly, miR-J1-5p expression was present in all fecal samples, but expression was lower in CRCs compared to controls or adenoma patients. Conclusion: JC virus-specific miR-J1-5p miRNA is a potential biomarker for viral infection, and the lower expression in patients with colonic neoplasia highlights its biological role regulating oncogenic T-Ag expression in CRC. Impact: JCV-specific miRNA is a candidate for the development of a non-invasive screening test, as well as therapeutic intervention for JCV-associated diseases.

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