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

MicroRNA miR-J1-5p as a potential biomarker for JC virus infection in the gastrointestinal tract.
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DOI:
10.1371/journal.pone.0100036
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Goel A
Goel A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Link A;Balaguer F;Nagasaka T;Boland CR;Goel A

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JC 病毒 (JCV) 是一种人类多瘤病毒,可引起进行性多灶性白质脑病 (PML),与结直肠癌 (CRC) 相关。然而,确定 JCV 感染及其在致癌作用中的作用一直具有挑战性,这凸显了对该病毒更好的诊断策略的需要。 JCV 特异性 microRNA (miRNA) 已被鉴定并显示出对致癌 JCV T-Ag 具有负调节作用。在此,我们确定了健康受试者和 CRC 患者临床标本中 JCV miRNA 的表达模式。 JCV miRNA 表达在用 JCV T-Ag 转染的 CRC 细胞系中得到验证。使用表达 T-Ag 的 CRC 组织证实了结果。在健康志愿者的新鲜粪便样本、健康受试者和结直肠肿瘤患者的粪便潜血检测试剂盒样本中测量了 JCV 特异性 miR-J1-5p 的表达。 JCV miR-J1-5p 在 JCV 转染的 CRC 细胞中检测到,但在载体转染的 CRC 细胞中未检测到,并且在细胞传代之间保持稳定。 MiR-J1-5p 存在于所有六个 JCV T-Ag+ CRC 样本中。令人惊讶的是,JCV miRNA 在所有正常组织中均可检测到,但在 CRC 组织中的表达要低得多。同样,miR-J1-5p 表达存在于所有粪便样本中,但与对照或腺瘤患者相比,CRC 中的表达较低。 JC 病毒特异性 miR-J1-5p miRNA 是病毒感染的潜在生物标志物,结肠肿瘤患者中的较低表达凸显了其调节 CRC 中致癌 T-Ag 表达的生物学作用。 JCV 特异性 miRNA 是开发非侵入性筛查测试以及 JCV 相关疾病治疗干预的候选者。
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. 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. 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. 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. 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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