Gao Jing, Yu Gang, Yan Yan, Hu Weifeng, Hu Dayong, Wang Weibing, Yang Guoxian, Wei Jing, Yang Shiquan
Department of General Practice, Xujiahui Community Healthcare Center of Xuhui District of Shanghai, Shanghai 200030, P.R. China.
Department of Nephrology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, P.R. China.
Exp Ther Med. 2024 Jul 16;28(3):368. doi: 10.3892/etm.2024.12657. eCollection 2024 Sep.
Renal cell carcinoma (RCC) is a common malignancy of the urinary system. Although traditional therapies, such as surgery assisted with chemotherapy have improved the quality of life and survival time of patients with RCC, patients with metastasis or recurrence benefit little from such therapies. At present, little is known about the underlying mechanisms of RCC, rendering treatment selection and implementation challenging. Therefore, investigating the cause and underlying mechanisms of RCC remain of importance to explore potential new avenues for its treatment. Inter-α-trypsin inhibitor heavy chain 1 () is an inflammation-associated gene reported to suppress the progression of liver cancer. However, its role in RCC remains poorly understood. Therefore, the present study aimed to investigate the role and mechanism of ITIH1 in RCC. Based on data obtained from The Cancer Genome Atlas database, ITIH1 expression was demonstrated to be significantly higher in tumor tissues compared with normal tissues, which was in turn negatively associated with the survival of patients with RCC. However, in RCC cells, ITIH1 was shown to be expressed at significantly lower levels compared with those in HK-2 cells. The discrepancy between tissues and cell lines might be due to the different environment of cell growth. ITIH1 knockdown in RCC cells significantly increased cell proliferation and invasion whilst significantly decreasing the apoptosis rate, compared with those in control cells (without ITIH1 knockdown). By contrast, overexpression of ITIH1 significantly inhibited cell proliferation and invasion in RCC cells. In terms of western blotting results, the phosphorylation levels of NF-κB were significantly increased following ITIH1 knockdown. The protein expression level of IκB significantly decreased whereas that of IKK, Cyclin D1, proliferating cell nuclear antigen and α-smooth muscle actin were significantly increased in ITIH1-knockdown cells, compared with those in the control cells (without ITIH1 knockdown). This suggests that the NF-κB pathway may be activated after ITIH1 knockdown. Following treatment with the NF-κB pathway inhibitor JSH-23 in combination with ITIH1 knockdown, RCC cell proliferation and invasion were significantly reduced compared with those after ITIH1 knockdown alone. In summary, results from the present study suggest that ITIH1 can serve an inhibitory role in the progression of RCC, which could potentially be inhibited through the NF-κB signaling pathway.
肾细胞癌（RCC）是泌尿系统常见的恶性肿瘤。尽管传统疗法，如手术辅助化疗改善了RCC患者的生活质量和生存时间，但发生转移或复发的患者从这类疗法中获益甚微。目前，对RCC的潜在机制了解甚少，这使得治疗方案的选择和实施具有挑战性。因此，研究RCC的病因和潜在机制对于探索其潜在的新治疗途径仍然很重要。间α-胰蛋白酶抑制剂重链1（ITIH1）是一种与炎症相关的基因，据报道可抑制肝癌的进展。然而，其在RCC中的作用仍知之甚少。因此，本研究旨在探讨ITIH1在RCC中的作用及机制。基于从癌症基因组图谱数据库获得的数据，与正常组织相比，ITIH1在肿瘤组织中的表达显著更高，这反过来又与RCC患者的生存率呈负相关。然而，在RCC细胞中，与HK-2细胞相比，ITIH1的表达水平显著更低。组织和细胞系之间的差异可能是由于细胞生长环境不同。与对照细胞（未敲低ITIH1）相比，RCC细胞中ITIH1敲低显著增加了细胞增殖和侵袭，同时显著降低了细胞凋亡率。相比之下，ITIH1的过表达显著抑制了RCC细胞的增殖和侵袭。就蛋白质印迹结果而言，ITIH1敲低后NF-κB的磷酸化水平显著增加。与对照细胞（未敲低ITIH1）相比，ITIH1敲低细胞中IκB的蛋白质表达水平显著降低，而IKK、细胞周期蛋白D1、增殖细胞核抗原和α-平滑肌肌动蛋白的表达水平显著增加。这表明ITIH1敲低后NF-κB通路可能被激活。在用NF-κB通路抑制剂JSH-23联合ITIH1敲低处理后，与单独ITIH1敲低相比，RCC细胞增殖和侵袭显著降低。总之，本研究结果表明ITIH1在RCC进展中可发挥抑制作用，这可能通过NF-κB信号通路被抑制。
