{"title":"IFI30 Knockdown Inhibits ESCC Progression by Promoting Apoptosis and Senescence via Activation of JNK and P21/P16 Pathways.","authors":"Wenyao Xie, Sisi Wei, Caiting Feng, Yuhui Fu, Zhe Zhang, Suli Dai, Cong Zhang, Lianmei Zhao, Baoen Shan","doi":"10.1111/1759-7714.70063","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly cancer, making it essential to understand the molecular mechanisms influencing its development and prognosis. The role of interferon-gamma-inducible protein 30 (IFI30) in antigen processing is well-established, but its impact on the progression of ESCC remains unclear. This study aimed to investigate the biological function and potential mechanisms of IFI30 in ESCC progression.</p><p><strong>Methods: </strong>Public databases, proteomics, and immunohistochemistry (IHC) were employed to analyze IFI30 expression. Cell proliferation, migration, and invasion were evaluated using MTS, colony formation, wound healing, and transwell assays. Nude mouse xenograft models were established to assess the effects of IFI30 knockdown in vivo. Quantitative proteomics was utilized to identify differentially expressed proteins (DEPs) and pathways altered by IFI30 knockdown. Cell apoptosis and senescence were evaluated by flow cytometry, SA-β-gal staining, and reactive oxygen species (ROS) analysis.</p><p><strong>Results: </strong>IFI30 was highly expressed in ESCC and was correlated with advanced stage and poor prognosis. IFI30 knockdown inhibited ESCC cell proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo. DEPs were mainly enriched in biological pathways related to apoptosis, mitophagy, cellular senescence, and lysosome. Furthermore, IFI30 knockdown in ESCC cells upregulated HRAS expression, increased ROS production, activated the JNK signaling pathway, and elevated the expression of P16 and P21, thereby promoting apoptosis and senescence.</p><p><strong>Conclusions: </strong>This study suggests that IFI30 may regulate the JNK and P21/P16 pathways, exerting pro-tumorigenic effects in ESCC. IFI30 could serve as a potential novel target for ESCC treatment.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":"16 7","pages":"e70063"},"PeriodicalIF":2.3000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971534/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Thoracic Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/1759-7714.70063","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly cancer, making it essential to understand the molecular mechanisms influencing its development and prognosis. The role of interferon-gamma-inducible protein 30 (IFI30) in antigen processing is well-established, but its impact on the progression of ESCC remains unclear. This study aimed to investigate the biological function and potential mechanisms of IFI30 in ESCC progression.
Methods: Public databases, proteomics, and immunohistochemistry (IHC) were employed to analyze IFI30 expression. Cell proliferation, migration, and invasion were evaluated using MTS, colony formation, wound healing, and transwell assays. Nude mouse xenograft models were established to assess the effects of IFI30 knockdown in vivo. Quantitative proteomics was utilized to identify differentially expressed proteins (DEPs) and pathways altered by IFI30 knockdown. Cell apoptosis and senescence were evaluated by flow cytometry, SA-β-gal staining, and reactive oxygen species (ROS) analysis.
Results: IFI30 was highly expressed in ESCC and was correlated with advanced stage and poor prognosis. IFI30 knockdown inhibited ESCC cell proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo. DEPs were mainly enriched in biological pathways related to apoptosis, mitophagy, cellular senescence, and lysosome. Furthermore, IFI30 knockdown in ESCC cells upregulated HRAS expression, increased ROS production, activated the JNK signaling pathway, and elevated the expression of P16 and P21, thereby promoting apoptosis and senescence.
Conclusions: This study suggests that IFI30 may regulate the JNK and P21/P16 pathways, exerting pro-tumorigenic effects in ESCC. IFI30 could serve as a potential novel target for ESCC treatment.
期刊介绍：
Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society.
The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
