Lv Geni, Chen Juan, Wei Dan, Zhang Wenzhe, Xie Wanhui, Yang Shuanying
Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Road, Xingcheng District, Xi'an, 710004 Shaanxi China.
Department of Respiratory Medicine, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, China.
Cytotechnology. 2025 Aug;77(4):138. doi: 10.1007/s10616-025-00804-9. Epub 2025 Jul 5.
The progression of cancer is remarkable for its ability to evade the immune system. SPOCK1 plays crucial roles in lung carcinoma malignant phenotypes and CD8 + T cell infiltration. Here, we looked at how SPOCK1 drives immune evasion in lung cancer and unraveled the underlying mechanisms. Expression analyses were performed using quantitative PCR (qPCR), immunoblotting, or immunohistochemistry (IHC). Cell proliferation and viability were assessed by MTT assay. Cell apoptosis, invasion, and sphere formation were evaluated. The POU2F1-SPOCK1 relationship was analyzed by luciferase and ChIP assays. The ELAVL1-SPOCK1 relationship was verified by SPOCK1 mRNA stability analysis. In vivo validation of the POU2F1-SPOCK1 axis was performed using xenograft assays along with lentiviral rescue approach. Increased levels of SPOCK1 predicted poor clinical outcomes in lung carcinoma patients (n = 39) and were associated with PDL1 expression and the tumor mutational burden (TMB). SPOCK1 depletion suppressed the growth, invasion, and stemness of lung cancer cells. Moreover, SPOCK1 depletion increased TNF-α and IFN-γ secretion, enhanced CD8 + T cell viability, and suppressed CD8 + T cell apoptosis in vitro. Mechanistically, POU2F1 transcriptionally controlled SPOCK1 expression. SPOCK1 restoration reversed the impact of POU2F1 depletion on cancer cell malignant phenotypes and tumor immune evasion. Furthermore, ELAVL1 increased SPOCK1 mRNA stability to upregulate SPOCK1. Additionally, SPOCK1 increase rescued the growth of POU2F1-depleted A549 xenografts in vivo (n = 5 per group). Our findings demonstrate that SPOCK1 upregulation induced by POU2F1 or ELAVL1 contributes to lung carcinoma progression by sustaining cancer cell malignant phenotypes and promoting immune evasion, suggesting SPOCK1 as a potential target for lung cancer therapy.
The online version contains supplementary material available at 10.1007/s10616-025-00804-9.
癌症的进展以其逃避免疫系统的能力而显著。SPOCK1在肺癌恶性表型和CD8 + T细胞浸润中起关键作用。在此，我们研究了SPOCK1如何驱动肺癌中的免疫逃逸并揭示了其潜在机制。使用定量PCR（qPCR）、免疫印迹或免疫组织化学（IHC）进行表达分析。通过MTT法评估细胞增殖和活力。评估细胞凋亡、侵袭和球体形成。通过荧光素酶和ChIP分析分析POU2F1-SPOCK1关系。通过SPOCK1 mRNA稳定性分析验证ELAVL1-SPOCK1关系。使用异种移植试验和慢病毒拯救方法对POU2F1-SPOCK1轴进行体内验证。SPOCK1水平升高预示着肺癌患者（n = 39）的临床预后不良，并且与PDL1表达和肿瘤突变负担（TMB）相关。SPOCK1缺失抑制了肺癌细胞的生长、侵袭和干性。此外，SPOCK1缺失增加了TNF-α和IFN-γ分泌，增强了CD8 + T细胞活力，并在体外抑制了CD8 + T细胞凋亡。机制上，POU2F1转录控制SPOCK1表达。SPOCK1恢复逆转了POU2F1缺失对癌细胞恶性表型和肿瘤免疫逃逸的影响。此外，ELAVL1增加SPOCK1 mRNA稳定性以上调SPOCK1。此外，SPOCK1增加挽救了体内POU2F1缺失的A549异种移植瘤的生长（每组n = 5）。我们的研究结果表明，由POU2F1或ELAVL1诱导的SPOCK1上调通过维持癌细胞恶性表型和促进免疫逃逸促进肺癌进展，提示SPOCK1作为肺癌治疗的潜在靶点。
在线版本包含可在10.1007/s10616-025-00804-9获取的补充材料。
