Guosheng Tan1, Binhui Xie2, Na Yu1, Jianwen Huang3, Bing Zhang4, Fangzeng Lin1, Heping Li5. 1. Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China. 2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People's Republic of China. 3. Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China. 4. Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China. 5. Department of Medical Oncology of the Eastern Hospital, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China. drliheping@163.com.
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the worldwide. Sorafenib is approved for first-line therapy against advanced HCC, but chemo-resistance is still a leading cause of tumor relapse and treatment failure in HCC. Thus, there is a significant clinical need to identify effective strategies to overcome drug resistance on the disease. METHODS: The protein and mRNA expression of TRIM37 in HCC cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. HCC tissue samples were analyzed by IHC to investigate the association between TRIM37expression and the clinicopathological characteristics of HCC patients. Functional assays, such as MTT, FACS, and Tunel assay, are used to determine the oncogenic role of TRIM37 in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37promotes chemoresistance in HCC. RESULTS: We found that both the mRNA and protein expression of TRIM37 was markedly upregulated in HCC cell lines and tissues, especially in Sorafenib-resistance HCC tissues. Moreover, high TRIM37 expression was associated with poor prognosis with HCC patients. TRIM37 overexpression confers Sorafenib resistance on HCC cells; however, inhibition of TRIM37 sensitized HCC cell lines to Sorafenib cytotoxicity. Additionally, TRIM37 upregulated the levels of AKT activity and phosphorylated AKT, thereby activating canonical AKT signaling. CONCLUSION: Our findings suggest that targeting TRIM37 signaling may represent a promising strategy to enhance Sorafenib response in HCC patients with chemoresistant.
BACKGROUND:Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the worldwide. Sorafenib is approved for first-line therapy against advanced HCC, but chemo-resistance is still a leading cause of tumor relapse and treatment failure in HCC. Thus, there is a significant clinical need to identify effective strategies to overcome drug resistance on the disease. METHODS: The protein and mRNA expression of TRIM37 in HCC cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. HCC tissue samples were analyzed by IHC to investigate the association between TRIM37expression and the clinicopathological characteristics of HCC patients. Functional assays, such as MTT, FACS, and Tunel assay, are used to determine the oncogenic role of TRIM37 in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37promotes chemoresistance in HCC. RESULTS: We found that both the mRNA and protein expression of TRIM37 was markedly upregulated in HCC cell lines and tissues, especially in Sorafenib-resistance HCC tissues. Moreover, high TRIM37 expression was associated with poor prognosis with HCC patients. TRIM37 overexpression confers Sorafenib resistance on HCC cells; however, inhibition of TRIM37 sensitized HCC cell lines to Sorafenibcytotoxicity. Additionally, TRIM37 upregulated the levels of AKT activity and phosphorylated AKT, thereby activating canonical AKT signaling. CONCLUSION: Our findings suggest that targeting TRIM37 signaling may represent a promising strategy to enhance Sorafenib response in HCC patients with chemoresistant.
Authors: Lingyun Wu; Xin Yin; Kan Jiang; Jie Yin; Hao Yu; Lingling Yang; Chiyuan Ma; Senxiang Yan Journal: Cancer Med Date: 2022-02-09 Impact factor: 4.452