pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation
Abstract Hepatocellular carcinoma (HCC) is a global health concern, ranking as the fourth leading cause of cancer-related deaths worldwide. However, the role of piwi-interacting RNAs (piRNAs) in HCC processes has not been extensively explored. Through small RNA sequencing, our study identified a spe...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-024-02285-9 |
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| author | Zhouxiang Liao Lichao Yang Xiaojing Cheng Xuejing Huang Qi Zhang Daoqiang Wen Zhenyu Song Yasi Li Sha Wen Yongfeng Li Meizhen Ou Zhangnan Huang Tianqi Liu Min He |
| author_facet | Zhouxiang Liao Lichao Yang Xiaojing Cheng Xuejing Huang Qi Zhang Daoqiang Wen Zhenyu Song Yasi Li Sha Wen Yongfeng Li Meizhen Ou Zhangnan Huang Tianqi Liu Min He |
| author_sort | Zhouxiang Liao |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) is a global health concern, ranking as the fourth leading cause of cancer-related deaths worldwide. However, the role of piwi-interacting RNAs (piRNAs) in HCC processes has not been extensively explored. Through small RNA sequencing, our study identified a specific piRNA, pir-hsa-216911, which is highly expressed in HCC cells. This overexpression of pir-hsa-216911 promotes HCC cell invasion and inhibits cell death, particularly pyroptosis. Knocking out pir-hsa-216911 led to increased cell pyroptosis activity, resulting in the activation of caspase-1 and GSDMD. Further analysis revealed that pir-hsa-216911 targets and suppresses TLR4, a key gene associated with pyroptosis in HCC. In the Huh7 cell line, pir-hsa-216911 knockout confirmed its role in suppressing the TLR4/NFκB/NLRP3 pathway by silencing TLR4. Knocking out pir-hsa-216911 significantly inhibited the formation of Huh7 xenograft tumor. In HCC patients, pir-hsa-216911 was highly expressed in HCC tumor samples with steatosis, suppressing TLR4 expression and inhibiting GSDMD activation. This study introduces pir-hsa-216911 as a new high-expressing piRNA in HCC, which inhibits pyroptosis by silencing TLR4 to suppress GSDMD activation. These findings have significant implications for HCC molecular subtyping and as a potential target for cancer therapy. |
| format | Article |
| id | doaj-art-99b770cf90924229b9e287f4ce5690e7 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-99b770cf90924229b9e287f4ce5690e72025-01-19T12:10:32ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111310.1038/s41420-024-02285-9pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activationZhouxiang Liao0Lichao Yang1Xiaojing Cheng2Xuejing Huang3Qi Zhang4Daoqiang Wen5Zhenyu Song6Yasi Li7Sha Wen8Yongfeng Li9Meizhen Ou10Zhangnan Huang11Tianqi Liu12Min He13School of Public Health, Guangxi Medical UniversityLaboratory Animal Center of Guangxi Medical UniversitySchool of Public Health, Guangxi Medical UniversityLaboratory Animal Center of Guangxi Medical UniversityLaboratory Animal Center of Guangxi Medical UniversityDepartment of Hepatobiliary Surgery, The People’s Hospital of Guangxi Zhuang Autonomous RegionLaboratory Animal Center of Guangxi Medical UniversityDepartment of Public Health Sciences, College of Medicine, Pennsylvania State UniversityLaboratory Animal Center of Guangxi Medical UniversitySchool of Public Health, Guangxi Medical UniversityLaboratory Animal Center of Guangxi Medical UniversityDepartment of Hepatobiliary Surgery, The People’s Hospital of Guangxi Zhuang Autonomous RegionDepartment of Hepatobiliary Surgery, Hospital of Guangxi Jiang BingSchool of Public Health, Guangxi Medical UniversityAbstract Hepatocellular carcinoma (HCC) is a global health concern, ranking as the fourth leading cause of cancer-related deaths worldwide. However, the role of piwi-interacting RNAs (piRNAs) in HCC processes has not been extensively explored. Through small RNA sequencing, our study identified a specific piRNA, pir-hsa-216911, which is highly expressed in HCC cells. This overexpression of pir-hsa-216911 promotes HCC cell invasion and inhibits cell death, particularly pyroptosis. Knocking out pir-hsa-216911 led to increased cell pyroptosis activity, resulting in the activation of caspase-1 and GSDMD. Further analysis revealed that pir-hsa-216911 targets and suppresses TLR4, a key gene associated with pyroptosis in HCC. In the Huh7 cell line, pir-hsa-216911 knockout confirmed its role in suppressing the TLR4/NFκB/NLRP3 pathway by silencing TLR4. Knocking out pir-hsa-216911 significantly inhibited the formation of Huh7 xenograft tumor. In HCC patients, pir-hsa-216911 was highly expressed in HCC tumor samples with steatosis, suppressing TLR4 expression and inhibiting GSDMD activation. This study introduces pir-hsa-216911 as a new high-expressing piRNA in HCC, which inhibits pyroptosis by silencing TLR4 to suppress GSDMD activation. These findings have significant implications for HCC molecular subtyping and as a potential target for cancer therapy.https://doi.org/10.1038/s41420-024-02285-9 |
| spellingShingle | Zhouxiang Liao Lichao Yang Xiaojing Cheng Xuejing Huang Qi Zhang Daoqiang Wen Zhenyu Song Yasi Li Sha Wen Yongfeng Li Meizhen Ou Zhangnan Huang Tianqi Liu Min He pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation Cell Death Discovery |
| title | pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation |
| title_full | pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation |
| title_fullStr | pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation |
| title_full_unstemmed | pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation |
| title_short | pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation |
| title_sort | pir hsa 216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing tlr4 initiated gsdmd activation |
| url | https://doi.org/10.1038/s41420-024-02285-9 |
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