Abstract
IntroductionJC 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 MethodsJCV 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.ResultsJCV 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.ConclusionJC 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.ImpactJCV-specific miRNA is a candidate for the development of a non-invasive screening test, as well as therapeutic intervention for JCV-associated diseases.
Highlights
JC virus (JCV), a human polyomavirus that causes progressive multifocal leukoencephalopathy (PML), has been linked to colorectal cancer (CRC)
JCV miRNA was detectable in all normal tissues, but the expression was much lower in CRC tissues
MiR-J1-5p expression was present in all fecal samples, but expression was lower in CRCs compared to controls or adenoma patients
Summary
JC virus (JCV), a human polyomavirus that causes progressive multifocal leukoencephalopathy (PML), has been linked to colorectal cancer (CRC). JC virus (JCV) is a human polyomavirus known for over 40 years as a causative agent for a fatal demyelinating disease called progressive multifocal leukoencephalopathy (PML) [1], but more recently it has been implicated in carcinogenesis. We evaluated the expression of miR-J15p in CRC tissues and stool samples from healthy subjects and patients with colorectal adenomas and cancers. Results from this preliminary study suggest a potential role of JCV-specific miR-J15p as a novel biomarker for JCV infection in the colon
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