SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway
Hepatitis C virus (HCV) infection involves a variety of viral and host factors, some of which promote the infection process. A small nucleolar RNA, C/D box 126 (SNORD126), was previously shown to be associated with hepatocellular carcinoma (HCC). However, the role of SNORD126 in HCV infection, which...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-09-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.565590/full |
| _version_ | 1818308915923779584 |
|---|---|
| author | Xijing Qian Chen Xu Bingan Wu Hailin Tang Ping Zhao Zhongtian Qi |
| author_facet | Xijing Qian Chen Xu Bingan Wu Hailin Tang Ping Zhao Zhongtian Qi |
| author_sort | Xijing Qian |
| collection | DOAJ |
| description | Hepatitis C virus (HCV) infection involves a variety of viral and host factors, some of which promote the infection process. A small nucleolar RNA, C/D box 126 (SNORD126), was previously shown to be associated with hepatocellular carcinoma (HCC). However, the role of SNORD126 in HCV infection, which is one of the primary reasons for HCC development, has not been elucidated. In the present study, using small nucleolar RNA profiling, we observed that SNORD126 was significantly downregulated during HCV infection in both Huh7 and Huh7.5.1 cells. In addition, overexpression of SNORD126 enhanced HCV entry into host cells, whereas SNORD126 knockdown showed the opposite effect, suggesting that SNORD126 promotes HCV infection, especially through viral entry. Further functional analysis revealed that SNORD126 could enhance the expression level of claudin-1 (CLDN1), a key HCV entry factor, by increasing the levels of phosphorylated AKT. Additionally, the function of SNORD126 in HCV infection was associated with ribonucleoprotein (RNP) complexes. In summary, our findings demonstrate that oncogenic SNORD126 levels are decreased during HCV infection probably due to the host defense reaction, and SNORD126 may be important to promote viral entry by increasing CLDN1 expression through activation of the PI3K-AKT pathway, the mechanism of which is partly associated with SNORD126-mediated snoRNA RNP (snoRNP) function. Our work here provides initial evidence that endogenous snoRNA takes part in HCV infection and shows potential as a diagnostic or antiviral agent. |
| first_indexed | 2024-12-13T07:21:52Z |
| format | Article |
| id | doaj.art-f0d99b5c4f4445dbaded463496427eae |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T07:21:52Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f0d99b5c4f4445dbaded463496427eae2022-12-21T23:55:25ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-09-011110.3389/fmicb.2020.565590565590SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling PathwayXijing Qian0Chen Xu1Bingan Wu2Hailin Tang3Ping Zhao4Zhongtian Qi5Department of Microbiology, Second Military Medical University, Shanghai, ChinaSpine Center, Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, ChinaDepartment of Microbiology, Second Military Medical University, Shanghai, ChinaDepartment of Microbiology, Second Military Medical University, Shanghai, ChinaDepartment of Microbiology, Second Military Medical University, Shanghai, ChinaDepartment of Microbiology, Second Military Medical University, Shanghai, ChinaHepatitis C virus (HCV) infection involves a variety of viral and host factors, some of which promote the infection process. A small nucleolar RNA, C/D box 126 (SNORD126), was previously shown to be associated with hepatocellular carcinoma (HCC). However, the role of SNORD126 in HCV infection, which is one of the primary reasons for HCC development, has not been elucidated. In the present study, using small nucleolar RNA profiling, we observed that SNORD126 was significantly downregulated during HCV infection in both Huh7 and Huh7.5.1 cells. In addition, overexpression of SNORD126 enhanced HCV entry into host cells, whereas SNORD126 knockdown showed the opposite effect, suggesting that SNORD126 promotes HCV infection, especially through viral entry. Further functional analysis revealed that SNORD126 could enhance the expression level of claudin-1 (CLDN1), a key HCV entry factor, by increasing the levels of phosphorylated AKT. Additionally, the function of SNORD126 in HCV infection was associated with ribonucleoprotein (RNP) complexes. In summary, our findings demonstrate that oncogenic SNORD126 levels are decreased during HCV infection probably due to the host defense reaction, and SNORD126 may be important to promote viral entry by increasing CLDN1 expression through activation of the PI3K-AKT pathway, the mechanism of which is partly associated with SNORD126-mediated snoRNA RNP (snoRNP) function. Our work here provides initial evidence that endogenous snoRNA takes part in HCV infection and shows potential as a diagnostic or antiviral agent.https://www.frontiersin.org/article/10.3389/fmicb.2020.565590/fullsmall nucleolar RNAnon-coding RNASNORD126hepatitis C virusclaudin-1viral entry |
| spellingShingle | Xijing Qian Chen Xu Bingan Wu Hailin Tang Ping Zhao Zhongtian Qi SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway Frontiers in Microbiology small nucleolar RNA non-coding RNA SNORD126 hepatitis C virus claudin-1 viral entry |
| title | SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway |
| title_full | SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway |
| title_fullStr | SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway |
| title_full_unstemmed | SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway |
| title_short | SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway |
| title_sort | snord126 promotes hepatitis c virus infection by upregulating claudin 1 via activation of pi3k akt signaling pathway |
| topic | small nucleolar RNA non-coding RNA SNORD126 hepatitis C virus claudin-1 viral entry |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.565590/full |
| work_keys_str_mv | AT xijingqian snord126promoteshepatitiscvirusinfectionbyupregulatingclaudin1viaactivationofpi3kaktsignalingpathway AT chenxu snord126promoteshepatitiscvirusinfectionbyupregulatingclaudin1viaactivationofpi3kaktsignalingpathway AT binganwu snord126promoteshepatitiscvirusinfectionbyupregulatingclaudin1viaactivationofpi3kaktsignalingpathway AT hailintang snord126promoteshepatitiscvirusinfectionbyupregulatingclaudin1viaactivationofpi3kaktsignalingpathway AT pingzhao snord126promoteshepatitiscvirusinfectionbyupregulatingclaudin1viaactivationofpi3kaktsignalingpathway AT zhongtianqi snord126promoteshepatitiscvirusinfectionbyupregulatingclaudin1viaactivationofpi3kaktsignalingpathway |