Xie Wenyao, Wei Sisi, Feng Caiting, Fu Yuhui, Zhang Zhe, Dai Suli, Zhang Cong, Zhao Lianmei, Shan Baoen
Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Oncology, Handan Central Hospital, Handan, China.
Thorac Cancer. 2025 Apr;16(7):e70063. doi: 10.1111/1759-7714.70063.
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.
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.
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.
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.
食管鳞状细胞癌（ESCC）是一种常见且致命的癌症，因此了解影响其发生发展和预后的分子机制至关重要。干扰素-γ诱导蛋白30（IFI30）在抗原加工中的作用已得到充分证实，但其对ESCC进展的影响仍不清楚。本研究旨在探讨IFI30在ESCC进展中的生物学功能及潜在机制。
利用公共数据库、蛋白质组学和免疫组织化学（IHC）分析IFI30的表达。采用MTS法、集落形成实验、伤口愈合实验和Transwell实验评估细胞增殖、迁移和侵袭能力。建立裸鼠异种移植模型以评估体内IFI30敲低的效果。利用定量蛋白质组学鉴定IFI30敲低后差异表达的蛋白质（DEPs）和改变的信号通路。通过流式细胞术、SA-β-半乳糖苷酶染色和活性氧（ROS）分析评估细胞凋亡和衰老。
IFI30在ESCC中高表达，且与晚期和预后不良相关。IFI30敲低在体外抑制ESCC细胞增殖、迁移和侵袭，并在体内抑制肿瘤生长。DEPs主要富集在与凋亡、线粒体自噬、细胞衰老和溶酶体相关的生物学通路中。此外，ESCC细胞中IFI30敲低下调HRAS表达，增加ROS产生，激活JNK信号通路，并上调P16和P21的表达，从而促进凋亡和衰老。
本研究表明IFI30可能通过调节JNK和P21/P16信号通路在ESCC中发挥促肿瘤作用。IFI30可能成为ESCC治疗的潜在新靶点。
