Introduction: Prostate cancer is the most common non-cutaneous male cancers, contributing to significant mortality rates globally. Mutations of RNase L, an enzyme involved in inflammatory and immunological pathways, h...Introduction: Prostate cancer is the most common non-cutaneous male cancers, contributing to significant mortality rates globally. Mutations of RNase L, an enzyme involved in inflammatory and immunological pathways, have been speculated to predispose to cancer. This study assesses three different mutations of the RNase L gene in Irish prostate cancer patients, including one linked with general cancer susceptibility never investigated before in prostate cancer (rs3738579), and reports on links with aggressive cancer. Methods: 134 patients had their RNase L mutation status determined by polymerase chain reaction (PCR) of serum DNA. Complementary clinical details for each patient are statistically analysed. Results: No link to age of diagnosis, high grade disease or prostate specific antigen (PSA) level at diagnosis was demonstrated with any of the studied single nucleotide polymorphisms (SNP). The SNP variation was consistent with that of published international series. Conclusion: SNP genotypic frequencies in Ireland are consistent with international findings. The studied RNase L mutations including rs3738579 do not appear to have a significant impact on our patient population.展开更多
Enterovirus 71(EV71) caused hand, foot and mouth disease(HFMD) is a serious threat to the health of young children. Although type I interferon(IFN-I) has been proven to control EV71 replication, the key downstream IFN...Enterovirus 71(EV71) caused hand, foot and mouth disease(HFMD) is a serious threat to the health of young children. Although type I interferon(IFN-I) has been proven to control EV71 replication, the key downstream IFNstimulated gene(ISG) remains to be clarified and investigated. Recently, we found that 2’-5’-oligoadenylate synthetases 3(OAS3), as one of ISG of IFN-β1b, was antagonized by EV71 3C protein. Here, we confirm that OAS3is the major determinant of IFN-β1b-mediated EV71 inhibition, which depends on the downstream constitutive RNase L activation. 2’-5’-oligoadenylate(2-5A) synthesis activity deficient mutations of OAS3 D816A, D818A,D888A, and K950A lost resistance to EV71 because they could not activate downstream RNase L. Further investigation proved that EV71 infection induced OAS3 but not RNase L expression by IFN pathway. Mechanically, EV71 or IFN-β1b-induced phosphorylation of STAT1, but not STAT3, initiated the transcription of OAS3 by directly binding to the OAS3 promoter. Our works elucidate the immune regulatory mechanism of the host OAS3/RNase L system against EV71 replication.展开更多
文摘Introduction: Prostate cancer is the most common non-cutaneous male cancers, contributing to significant mortality rates globally. Mutations of RNase L, an enzyme involved in inflammatory and immunological pathways, have been speculated to predispose to cancer. This study assesses three different mutations of the RNase L gene in Irish prostate cancer patients, including one linked with general cancer susceptibility never investigated before in prostate cancer (rs3738579), and reports on links with aggressive cancer. Methods: 134 patients had their RNase L mutation status determined by polymerase chain reaction (PCR) of serum DNA. Complementary clinical details for each patient are statistically analysed. Results: No link to age of diagnosis, high grade disease or prostate specific antigen (PSA) level at diagnosis was demonstrated with any of the studied single nucleotide polymorphisms (SNP). The SNP variation was consistent with that of published international series. Conclusion: SNP genotypic frequencies in Ireland are consistent with international findings. The studied RNase L mutations including rs3738579 do not appear to have a significant impact on our patient population.
基金supported by funding from the National Key R&D Program of China (2021YFC2301900 and 2301904)National Natural Science Foundation of China (81930062)+2 种基金Science and Technology Department of Jilin Province (YDZJ202201ZYTS590)Health Commission of Jilin Province (2020J059)the Key Laboratory of Molecular Virology,Jilin Province (20102209)
文摘Enterovirus 71(EV71) caused hand, foot and mouth disease(HFMD) is a serious threat to the health of young children. Although type I interferon(IFN-I) has been proven to control EV71 replication, the key downstream IFNstimulated gene(ISG) remains to be clarified and investigated. Recently, we found that 2’-5’-oligoadenylate synthetases 3(OAS3), as one of ISG of IFN-β1b, was antagonized by EV71 3C protein. Here, we confirm that OAS3is the major determinant of IFN-β1b-mediated EV71 inhibition, which depends on the downstream constitutive RNase L activation. 2’-5’-oligoadenylate(2-5A) synthesis activity deficient mutations of OAS3 D816A, D818A,D888A, and K950A lost resistance to EV71 because they could not activate downstream RNase L. Further investigation proved that EV71 infection induced OAS3 but not RNase L expression by IFN pathway. Mechanically, EV71 or IFN-β1b-induced phosphorylation of STAT1, but not STAT3, initiated the transcription of OAS3 by directly binding to the OAS3 promoter. Our works elucidate the immune regulatory mechanism of the host OAS3/RNase L system against EV71 replication.
