Dalian Medical University, Dalian, Liaoning, 116000, China.
Department of General Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, 213000, China.
Comb Chem High Throughput Screen. 2024;27(12):1758-1775. doi: 10.2174/0113862073254083231002052550.
INTRODUCTION: The role and prognostic value of POLA2 in liver cancer were comprehensively analyzed through TCGA, GEO, and ICGC databases, and the role of POLA2 in liver cancer cells and the regulatory mechanism involved were further verified through cell experiments. Hepatocellular carcinoma (HCC) is the most prevalent malignancy with high morbidity and mortality. Consequently, it is critical to identify robust and reliable predictive biomarkers and therapeutic targets for HCC patients. POLA2 is involved in the regulation of various tumors, but the specific role of POLA2 in HCC has not been reported. The regulatory role and prognostic value of POLA2 in HCC were determined by bioinformatics techniques and cell experiments. METHODS: The specific role and prognostic value of POLA2 in HCC were comprehensively analyzed by combining the expression data of POLA2 in TCGA, GEO, and ICGC databases and clinical data. In clinical samples, the expression of POLA2 in liver cancer was verified by QPCR. Further, the regulatory role of POLA2 in HCC was explored through cell experiments such as CCK-8, clonal formation experiment, EDU cell proliferation experiment, and flow cytometry. In terms of mechanism exploration, western blot was used to verify the specific regulatory mechanism that POLA2 participated in. Finally, the relationship between POLA2 and immune invasion of HCC was analyzed by using the TIMER database. RESULTS: A POLA2 expression and prognosis analysis of HCC patients was conducted using the TCGA, GEO, and ICGC databases. We hypothesized that POLA2 might be one of the key factors contributing to the HCC progression. According to a combined analysis of TCGA, ICGC, and GEO databases, POLA2 was highly expressed in HCC. This was further confirmed in clinical samples using the qPCR. POLA2 knockdown was also performed in vitro on HCC cell lines to study the changes in their biological behavior. We confirmed that POLA2 was associated with HCC proliferation by CCK-8, Colony Formation, and EDU assay. We verified the POLA2's involvement in cell cycle regulation using flow techniques. The relationship between POLA2 and PI3K/AKT/mTOR pathway was explored using Western Blotting experiments regarding its mechanism. Further analysis revealed that the POLA2 expression was significantly associated with HCC immune infiltration. CONCLUSION: Our study demonstrated POLA2's importance in HCC development and progression and its potential role as a biomarker for disease progression on multiple levels. POLA2 has an important role in regulating the cell cycle and cell proliferation. By interfering with the cell cycle and proliferation, HCC cell growth is inhibited. Furthermore, POLA2 expression was significantly associated with immune infiltration. POLA2 may play a role in HCC immunotherapy based on its correlation with several immune cell types' genetic markers. The findings of this study are expected to lead to new anticancer strategies for HCC.
简介：本研究通过 TCGA、GEO 和 ICGC 数据库全面分析了 POLA2 在肝癌中的作用和预后价值，并通过细胞实验进一步验证了 POLA2 在肝癌细胞中的作用及其涉及的调节机制。肝细胞癌（HCC）是发病率和死亡率最高的最常见恶性肿瘤。因此，识别 HCC 患者稳健可靠的预测生物标志物和治疗靶点至关重要。POLA2 参与多种肿瘤的调节，但 POLA2 在 HCC 中的具体作用尚未报道。本研究通过生物信息学技术和细胞实验确定了 POLA2 在 HCC 中的调节作用和预后价值。 方法：通过结合 TCGA、GEO 和 ICGC 数据库中 POLA2 的表达数据和临床数据，综合分析 POLA2 在 HCC 中的特定作用和预后价值。在临床样本中，通过 QPCR 验证 POLA2 在肝癌中的表达。进一步通过 CCK-8、克隆形成实验、EDU 细胞增殖实验和流式细胞术等细胞实验探索 POLA2 在 HCC 中的调节作用。在机制探索方面，使用 Western blot 验证 POLA2 参与的具体调节机制。最后，通过 TIMER 数据库分析 POLA2 与 HCC 免疫浸润的关系。 结果：通过 TCGA、GEO 和 ICGC 数据库对 HCC 患者的 POLA2 表达和预后进行分析。我们假设 POLA2 可能是 HCC 进展的关键因素之一。根据 TCGA、ICGC 和 GEO 数据库的综合分析，POLA2 在 HCC 中高表达。通过 qPCR 在临床样本中进一步证实了这一点。还在 HCC 细胞系上进行了体外 POLA2 敲低实验，以研究其生物学行为的变化。我们通过 CCK-8、集落形成和 EDU 测定证实了 POLA2 与 HCC 增殖有关。我们通过流式技术验证了 POLA2 参与细胞周期调控。通过 Western Blotting 实验探讨了其机制，探索了 POLA2 与 PI3K/AKT/mTOR 通路的关系。进一步分析表明，POLA2 的表达与 HCC 免疫浸润有显著相关性。 结论：本研究从多个层面证实了 POLA2 在 HCC 发生和发展中的重要作用及其作为疾病进展标志物的潜力。POLA2 在调节细胞周期和细胞增殖方面具有重要作用。通过干扰细胞周期和增殖，抑制 HCC 细胞生长。此外，POLA2 的表达与免疫浸润显著相关。基于其与几种免疫细胞类型遗传标志物的相关性，POLA2 可能在 HCC 免疫治疗中发挥作用。本研究的发现有望为 HCC 提供新的抗癌策略。
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