Abstract
The forkhead box (FOX) family of transcription factors are considered to have a role in tumorigenesis. FOXJ1 is a member of the FOX family; however, its function in human renal cell carcinoma (RCC) has remained to be elucidated. Therefore, the present study evaluated the expression of FOXJ1 in human clear cell RCC and the effect of FOXJ1 on the proliferative ability of RCC cells. The RCC specimens analyzed in the present study were obtained from 286 patients with RCC who underwent nephrectomy. FOXJ1 mRNA expression levels were determined using reverse transcription-quantitative polymerase chain reaction, and FOXJ1 protein expression levels were determined using immunohistochemistry and western blot analysis. To determine the effect of FOXJ1 on the proliferative ability of RCC cells, the expression of FOXJ1 was decreased using small interfering (si)RNA, and a FOXJ1 vector was stably transfected into RCC cell lines. The proliferative ability of RCC cells was then examined using a WST-1 assay and xenograft experiments with BALB/c nude mice, where the association between FOXJ1 expression and patient survival was determined using Kaplan-Meier analysis. FOXJ1 expression was significantly higher in RCC tissues compared with that of healthy renal tissues. Furthermore, FOXJ1 expression was associated with tumor stage, histologic grade and size. In addition, FOXJ1 significantly enhanced the proliferation of RCC cells in vitro and in vivo. The present study identified that FOXJ1 expression was upregulated in RCC and enhanced the proliferative ability of RCC cells. Therefore, FOXJ1 may serve as an independent prognostic marker and a therapeutic target for the treatment of patients with RCC.
Highlights
Human renal cell carcinoma (RCC) is the most common type of malignant kidney tumor in adults worldwide, and ~85% of RCCs are clear cell RCC (CCRCC) [1]
FOXO has been reported to be dysregulated in various types of tumor, including prostate and breast cancer, leukemia, glioblastoma and endometrial carcinoma [22,23,24,25,26,27,28]; FOXA1 was overexpressed in thyroid, lung and esophageal cancer [29,30]; and FOXC2 appears to be a key gene involved in tumor progression and angiogenesis [31]
The results indicated that FOXJ1 expression was significantly increased in CCRCC tissue compared with that of corresponding healthy kidney tissues, and FOXJ1 was expressed at levels similar to those detected by immunohistochemistry
Summary
Human renal cell carcinoma (RCC) is the most common type of malignant kidney tumor in adults worldwide, and ~85% of RCCs are clear cell RCC (CCRCC) [1]. Previous studies have determined that FOX proteins are associated with carcinogenesis and the progression of malignancies. The expression of FOXM1 was increased in a variety of types of tumor, including basal cell and hepatocellular carcinoma, as well as lung, breast, prostate and colorectal cancer [12,13,14,15,16,17]. A previous study proposed that FOXJ1 expression was decreased in breast cancer, functioning as a tumor suppressor gene [39]. The current study aimed to determine the expression of FOXJ1 in human RCC and its effect on the proliferative ability of human RCC cells. The immune complexes were evaluated using an enhanced chemiluminescence system (GE Healthcare Life Sciences, Chalfont, UK)
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