ITIH1 suppresses carcinogenesis in renal cell carcinoma through regulation of the NF‑&kappa;B signaling pathway

Gao,Jing; Yu,Gang; Yan,Yan; Hu,Weifeng; Hu,Dayong; Wang,Weibing; Yang,Guoxian; Wei,Jing; Yang,Shiquan

doi:10.3892/etm.2024.12657

ITIH1 suppresses carcinogenesis in renal cell carcinoma through regulation of the NF‑κB signaling pathway

Authors:
- Jing Gao
- Gang Yu
- Yan Yan
- Weifeng Hu
- Dayong Hu
- Weibing Wang
- Guoxian Yang
- Jing Wei
- Shiquan Yang
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Affiliations: 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, Department of Nephrology, Naval Medical Center of People's Liberation Army, Shanghai 200052, P.R. China, Department of Nephrology, The Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China, Department of Epidemiology, School of Public Health of Fudan University, Shanghai 200032, P.R. China
Published online on: July 16, 2024 https://doi.org/10.3892/etm.2024.12657
Article Number: 368

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Abstract

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 (ITIH1) 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.

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