Ornithine transcarbamylase downregulation is associated with poor prognosis in hepatocellular carcinoma

He,Lin; Cai,Xuefei; Cheng,Shengtao; Zhou,Hongzhong; Zhang,Zhenzhen; Ren,Jihua; Ren,Fang; Yang,Qiuxia; Tao,Nana; Chen,Juan

doi:10.3892/ol.2019.10174

Ornithine transcarbamylase downregulation is associated with poor prognosis in hepatocellular carcinoma

Authors:
- Lin He
- Xuefei Cai
- Shengtao Cheng
- Hongzhong Zhou
- Zhenzhen Zhang
- Jihua Ren
- Fang Ren
- Qiuxia Yang
- Nana Tao
- Juan Chen
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Affiliations: Key Laboratory of Molecular Biology of Infectious Diseases Designated by The Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Infectious Diseases, The Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China
Published online on: March 21, 2019 https://doi.org/10.3892/ol.2019.10174
Pages: 5030-5038
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‑associated mortalities worldwide. The role of ornithine transcarbamylase (OTC) in HCC remains unclear. In the present study, the expression of OTC in HCC was analyzed based on datasets from the Gene Expression Omnibus database of the National Center for Biotechnology Information and further confirmed by immunohistochemistry, western blotting analysis and reverse transcription‑quantitative polymerase chain reaction assays on clinical samples and cell lines. Furthermore, the associations between OTC expression and clinicopathological parameters as well as clinical outcome, including the overall and disease‑free survival rates were analyzed. Finally, the effect of OTC on HCC cells was measured using proliferation, bromodeoxyuridine and colony‑formation assays. Lower OTC expression was observed in HCC cells and tissues compared with primary human hepatocytes. Further investigation demonstrated that low expression of OTC in HCC was associated with larger tumor size and advanced grade. A Kaplan‑Meier analysis revealed that patients with lower levels of OTC exhibited shorter overall and disease‑free survival times. Notably, OTC silencing with RNA interference facilitated cell proliferation in HCC SK‑Hep‑1 and Huh‑7 cells. However, overexpression of OTC led to inhibition of cell proliferation. In conclusion, the present study identified a novel role of OTC in HCC development, providing a potential novel therapeutic target for this disease.

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