Abstract
The calpain 2 (CAPN2) is upregulated in various malignant carcinomas. Previous studies have reported that CAPN2 functioned as an oncogenic factor in human cancers. However, its clinical role and potential effects on cell metastasis and proliferation in renal cell carcinoma (RCC) remain unknown. In this study, we evaluated the mRNA and protein levels of CAPN2 in human RCC specimens, matched normal specimens, and RCC cell lines using quantitative Real-time PCR (RT-PCR) and western blot. Immunohistochemistry of 74 RCC tissues in a tissue microarrays (TMAs) and normal kidney tissues were performed. Kaplan-Meier survival curve analyses were conducted to measure the correlation between CAPN2 and tumor prognosis. Cell migration, invasion and proliferation were detected by transwell assays and Cell Counting Kit-8 (CCK-8) assays. CAPN2 exhibited a significant overexpression in human RCC tissues and cell lines compared with adjacent non-tumor tissues and normal human proximal tubule epithelial cell line HK-2. Strong staining of CAPN2 was associated with higher clinical stage and histological grade. In addition, sh-CAPN2 could significantly inhibit migration, invasion and proliferation of 769-P and CAKI-1 cells. Conversely, increased cell biological behaviors were observed in CAPN2-OV CAKI-2 cells. Moreover, the subsequent mechanism investigation suggested that CAPN2 promoted tumor progression by activating AKT/mTOR signaling, enhancing epithelial mesenchymal transition (EMT) and MMP9 levels. The present study indicates that CAPN2 may act as a prominent indicator for RCC progression and a novel therapeutic target for RCC patients.
Highlights
Renal cell carcinoma (RCC) is one of the commonest malignant tumors and comprises approximately 90% of kidney cancers [1]
Such meaningful connection was not observed between calpain 2 (CAPN2) expression and overall survival (OS) of renal cell carcinoma (RCC) patients (P = 0.102)
These results strongly suggested that CAPN2 might act as a crucial biomarker for RCC progression
Summary
Renal cell carcinoma (RCC) is one of the commonest malignant tumors and comprises approximately 90% of kidney cancers [1]. RCC represents only 2%– 3% of all cancers, a continuing rise in incidence has been observed with 63990 new estimated and 14400 death cases in the United States in 2017 [2, 3]. It is generally known that RCC is poorly responsive to conventional radiotherapy and chemotherapy contributed by multiple resistance. Molecular targeting agents such as tyrosine kinase inhibitors, antiangiogenic agents and immunotherapy have become the preferred standard approaches in RCC patients [7,8,9]. Multiple studies have detected numerous biomarkers which involved into cancer progression [12]. It is of great necessity to determine novel biomarkers and develop advanced therapeutic strategies for RCC patients
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