Hao Jiang1, Jing-Yuan Tang2, Dong Xue3, Yi-Meng Chen3, Ting-Chun Wu3, Qian-Feng Zhuang4, Xiao-Zhou He5. 1. Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China. 2. Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People's Republic of China. 3. Department of Urology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu, People's Republic of China. 4. Department of Urology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu, People's Republic of China. zhuangqianfeng19@163.com. 5. Department of Urology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu, People's Republic of China. czyyhxz@163.com.
Abstract
BACKGROUND: Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. Apolipoprotein C1 (APOC1) has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism. METHODS: Differential levels of APOC1 in RCC samples and normal tissues in a downloaded TCGA profile and clinical samples collected in our center were detected by quantitative reverse transcription PCR (qRT-PCR). The prognostic value of APOC1 in RCC was assessed by depicting Kaplan-Meier survival curves. After intervening APOC1 level by transfection of sh-APOC1 or oe-APOC1, changes in phenotypes of RCC cells were examined through CCK-8, colony formation, Transwell assay and flow cytometry. Subsequently, protein levels of EMT-related genes influenced by APOC1 were determined by Western blot. The involvement of the Wnt3a signaling in APOC1-regulated malignant process of RCC was then examined through a series of rescue experiments. Finally, a RCC xenograft model was generated in nude mice, aiming to further clarify the in vivo function of APOC1 in RCC process. RESULTS: APOC1 was upregulated in RCC samples. Notably, its level was correlated to overall survival of RCC patients, displaying a certain prognostic value. APOC1 was able to stimulate proliferative, migratory and invasive abilities in RCC cells. The Wnt3a signaling was identified to be involved in APOC1-mediated RCC process. Notably, Wnt3a was able to reverse the regulatory effects of APOC1 on RCC cell phenotypes. In vivo knockdown of APOC1 in xenografted nude mice slowed down the growth of RCC. CONCLUSIONS: APOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.
BACKGROUND:Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. Apolipoprotein C1 (APOC1) has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism. METHODS: Differential levels of APOC1 in RCC samples and normal tissues in a downloaded TCGA profile and clinical samples collected in our center were detected by quantitative reverse transcription PCR (qRT-PCR). The prognostic value of APOC1 in RCC was assessed by depicting Kaplan-Meier survival curves. After intervening APOC1 level by transfection of sh-APOC1 or oe-APOC1, changes in phenotypes of RCC cells were examined through CCK-8, colony formation, Transwell assay and flow cytometry. Subsequently, protein levels of EMT-related genes influenced by APOC1 were determined by Western blot. The involvement of the Wnt3a signaling in APOC1-regulated malignant process of RCC was then examined through a series of rescue experiments. Finally, a RCC xenograft model was generated in nude mice, aiming to further clarify the in vivo function of APOC1 in RCC process. RESULTS:APOC1 was upregulated in RCC samples. Notably, its level was correlated to overall survival of RCCpatients, displaying a certain prognostic value. APOC1 was able to stimulate proliferative, migratory and invasive abilities in RCC cells. The Wnt3a signaling was identified to be involved in APOC1-mediated RCC process. Notably, Wnt3a was able to reverse the regulatory effects of APOC1 on RCC cell phenotypes. In vivo knockdown of APOC1 in xenografted nude mice slowed down the growth of RCC. CONCLUSIONS:APOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.
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