Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C.
Despite advances in chronic hepatitis C treatment, a proportion of patients respond poorly to treatment. This study aimed to explore hepatic mRNA and microRNA signatures involved in hepatitis C treatment resistance. Global hepatic mRNA and microRNA expression profiles were compared using microarray...
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2014
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oai:doaj.org-article:3db261d955cf4f138548473a638d84232021-11-18T08:19:45ZInvolvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C.1932-620310.1371/journal.pone.0097078https://doaj.org/article/3db261d955cf4f138548473a638d84232014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24819603/?tool=EBIhttps://doaj.org/toc/1932-6203Despite advances in chronic hepatitis C treatment, a proportion of patients respond poorly to treatment. This study aimed to explore hepatic mRNA and microRNA signatures involved in hepatitis C treatment resistance. Global hepatic mRNA and microRNA expression profiles were compared using microarray data between treatment responses. Quantitative real-time polymerase chain reaction validated the gene signatures from 130 patients who were infected with hepatitis C virus genotype 1b and treated with pegylated interferon-alpha and ribavirin combination therapy. The correlation between mRNA and microRNA was evaluated using in silico analysis and in vitro siRNA and microRNA inhibition/overexpression experiments. Multivariate regression analysis identified that the independent variables IL28B SNP rs8099917, hsa-miR-122-5p, hsa-miR-17-5p, and MAP3K8 were significantly associated with a poor virologic response. MAP3K8 and miR-17-5p expression were inversely correlated with treatment response. Furthermore, miR-17-5p repressed HCV production by targeting MAP3K8. Collectively, the data suggest that several molecules and the inverse correlation between mRNA and microRNA contributed to a host genetic refractory hepatitis C treatment response.Akihito TsubotaKaoru MogushiHideki AizakiKen MiyaguchiKeisuke NagatsumaHiroshi MatsudairaTatsuya KushidaTomomi FurihataHiroshi TanakaTomokazu MatsuuraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e97078 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Akihito Tsubota Kaoru Mogushi Hideki Aizaki Ken Miyaguchi Keisuke Nagatsuma Hiroshi Matsudaira Tatsuya Kushida Tomomi Furihata Hiroshi Tanaka Tomokazu Matsuura Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C. |
| description |
Despite advances in chronic hepatitis C treatment, a proportion of patients respond poorly to treatment. This study aimed to explore hepatic mRNA and microRNA signatures involved in hepatitis C treatment resistance. Global hepatic mRNA and microRNA expression profiles were compared using microarray data between treatment responses. Quantitative real-time polymerase chain reaction validated the gene signatures from 130 patients who were infected with hepatitis C virus genotype 1b and treated with pegylated interferon-alpha and ribavirin combination therapy. The correlation between mRNA and microRNA was evaluated using in silico analysis and in vitro siRNA and microRNA inhibition/overexpression experiments. Multivariate regression analysis identified that the independent variables IL28B SNP rs8099917, hsa-miR-122-5p, hsa-miR-17-5p, and MAP3K8 were significantly associated with a poor virologic response. MAP3K8 and miR-17-5p expression were inversely correlated with treatment response. Furthermore, miR-17-5p repressed HCV production by targeting MAP3K8. Collectively, the data suggest that several molecules and the inverse correlation between mRNA and microRNA contributed to a host genetic refractory hepatitis C treatment response. |
| format |
article |
| author |
Akihito Tsubota Kaoru Mogushi Hideki Aizaki Ken Miyaguchi Keisuke Nagatsuma Hiroshi Matsudaira Tatsuya Kushida Tomomi Furihata Hiroshi Tanaka Tomokazu Matsuura |
| author_facet |
Akihito Tsubota Kaoru Mogushi Hideki Aizaki Ken Miyaguchi Keisuke Nagatsuma Hiroshi Matsudaira Tatsuya Kushida Tomomi Furihata Hiroshi Tanaka Tomokazu Matsuura |
| author_sort |
Akihito Tsubota |
| title |
Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C. |
| title_short |
Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C. |
| title_full |
Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C. |
| title_fullStr |
Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C. |
| title_full_unstemmed |
Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C. |
| title_sort |
involvement of map3k8 and mir-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis c. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/3db261d955cf4f138548473a638d8423 |
| work_keys_str_mv |
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