Abstract
BackgroundRenal 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.MethodsDifferential 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.ResultsAPOC1 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.ConclusionsAPOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.
Highlights
Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality
Expression characteristic and prognostic value of Apolipoprotein C1 (APOC1) in RCCA profile containing 523 cases of RCC and 100 cases of normal ones was downloaded from The Cancer Genome Atlas (TCGA) database
A worse overall survival was identified in RCC patients expressing high level of APOC1 (Fig. 1c)
Summary
Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism. Renal cell carcinoma (RCC) is a prevalent malignancy with relatively high rates of incidence and mortality. According to the histological classification, clear cell renal cell carcinoma (ccRcc) cases cover approximately 80% of RCC [2, 3]. Metastasis is the major reason for the poor prognosis of RCC. RCC metastases in the early phase remarkably limit the indications for operation, resulting in unsatisfactory clinical outcomes [7]. Molecular mechanisms underlying RCC metastasis remain largely unclear. Great efforts are required on searching effective and sensitive biomarkers for predicting the metastasis RCC in the early phase, enhancing the therapeutic efficacy on RCC patients
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