Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway
Abstract Background Interleukin-6 (IL-6) has been reported to be critical in oral squamous cell carcinoma (OSCC). However, the set of pathways that IL-6 might activate in OSCC are not fully understood. Methods IL-6 and Sox4 expressions were first determined with RT-qPCR, ELISA, Western blot, or immu...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-022-02376-4 |
| _version_ | 1811305843061161984 |
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| author | Li Xiao Xue Li Peilin Cao Wei Fei Hao Zhou Na Tang Yi Liu |
| author_facet | Li Xiao Xue Li Peilin Cao Wei Fei Hao Zhou Na Tang Yi Liu |
| author_sort | Li Xiao |
| collection | DOAJ |
| description | Abstract Background Interleukin-6 (IL-6) has been reported to be critical in oral squamous cell carcinoma (OSCC). However, the set of pathways that IL-6 might activate in OSCC are not fully understood. Methods IL-6 and Sox4 expressions were first determined with RT-qPCR, ELISA, Western blot, or immunohistochemistry in OSCC tissues, and correlations between IL-6 and Sox4 expression and patient pathological characteristics were examined, and Kaplan–Meier approach was employed for evaluating the prognostic utility in OSCC patients. CCK-8, EdU stain and colony formation assays were utilized to test cell proliferation in vitro. Mechanistically, downstream regulatory proteins of IL-6 were verified through chromatin immunoprecipitation, luciferase reporter, pull-down, and the rescued experiments. Western blot was used for detecting protein expression. A nude mouse tumorigenicity assay was used to confirm the role of IL-6 and Sox4 in vivo. Results IL-6 was upregulated in OSCC tissues, and Sox4 expression was positively correlated with IL-6 expression. High IL-6 and Sox4 expression was closely related to tumor size, TNM stage, and a poorer overall survival. Besides, IL-6 could accelerate OSCC cell proliferation by activating inflammasome via JAK2/STAT3/Sox4/NLRP3 pathways in vitro and in vivo. Furthermore, STAT3 played as a transcription factor which positively regulated Sox4, and IL-6 promotes Sox4 expression by activating JAK2/STAT3 pathway. Moreover, through the rescue experiments, we further confirmed that IL-6 could promote proliferation and NLRP3 inflammasome activation via JAK2/STAT3/Sox4 pathway in OSCC cells. Finally, knockdown of Sox4 suppressed OSCC growth in vivo, and antagonized the acceleration of IL-6 on tumor growth. Conclusions We confirmed that IL-6 plays an oncogenic role in OSCC progression by activating JAK2/STAT3/Sox4/NLRP3 pathway, which might be the therapeutic targets for OSCC remedy. |
| first_indexed | 2024-04-13T08:33:44Z |
| format | Article |
| id | doaj.art-b3d4bf23247e4f02acf6f71493f04ad6 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T08:33:44Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-b3d4bf23247e4f02acf6f71493f04ad62022-12-22T02:54:10ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662022-05-0141112010.1186/s13046-022-02376-4Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathwayLi Xiao0Xue Li1Peilin Cao2Wei Fei3Hao Zhou4Na Tang5Yi Liu6Department of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaAbstract Background Interleukin-6 (IL-6) has been reported to be critical in oral squamous cell carcinoma (OSCC). However, the set of pathways that IL-6 might activate in OSCC are not fully understood. Methods IL-6 and Sox4 expressions were first determined with RT-qPCR, ELISA, Western blot, or immunohistochemistry in OSCC tissues, and correlations between IL-6 and Sox4 expression and patient pathological characteristics were examined, and Kaplan–Meier approach was employed for evaluating the prognostic utility in OSCC patients. CCK-8, EdU stain and colony formation assays were utilized to test cell proliferation in vitro. Mechanistically, downstream regulatory proteins of IL-6 were verified through chromatin immunoprecipitation, luciferase reporter, pull-down, and the rescued experiments. Western blot was used for detecting protein expression. A nude mouse tumorigenicity assay was used to confirm the role of IL-6 and Sox4 in vivo. Results IL-6 was upregulated in OSCC tissues, and Sox4 expression was positively correlated with IL-6 expression. High IL-6 and Sox4 expression was closely related to tumor size, TNM stage, and a poorer overall survival. Besides, IL-6 could accelerate OSCC cell proliferation by activating inflammasome via JAK2/STAT3/Sox4/NLRP3 pathways in vitro and in vivo. Furthermore, STAT3 played as a transcription factor which positively regulated Sox4, and IL-6 promotes Sox4 expression by activating JAK2/STAT3 pathway. Moreover, through the rescue experiments, we further confirmed that IL-6 could promote proliferation and NLRP3 inflammasome activation via JAK2/STAT3/Sox4 pathway in OSCC cells. Finally, knockdown of Sox4 suppressed OSCC growth in vivo, and antagonized the acceleration of IL-6 on tumor growth. Conclusions We confirmed that IL-6 plays an oncogenic role in OSCC progression by activating JAK2/STAT3/Sox4/NLRP3 pathway, which might be the therapeutic targets for OSCC remedy.https://doi.org/10.1186/s13046-022-02376-4IL-6Oral squamous cell carcinomaNLRP3 inflammasomeJAK2STAT3Sox4 |
| spellingShingle | Li Xiao Xue Li Peilin Cao Wei Fei Hao Zhou Na Tang Yi Liu Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway Journal of Experimental & Clinical Cancer Research IL-6 Oral squamous cell carcinoma NLRP3 inflammasome JAK2 STAT3 Sox4 |
| title | Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway |
| title_full | Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway |
| title_fullStr | Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway |
| title_full_unstemmed | Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway |
| title_short | Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway |
| title_sort | interleukin 6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via jak2 stat3 sox4 nlrp3 signaling pathway |
| topic | IL-6 Oral squamous cell carcinoma NLRP3 inflammasome JAK2 STAT3 Sox4 |
| url | https://doi.org/10.1186/s13046-022-02376-4 |
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