Research Papers:
Overexpression of CAPN2 promotes cell metastasis and proliferation via AKT/mTOR signaling in renal cell carcinoma
Metrics: PDF 2068 views | HTML 3483 views | ?
Abstract
Chenkui Miao1,*, Chao Liang1,*, Ye Tian1,*, Aiming Xu1, Jundong Zhu1, Kai Zhao2, Jianzhong Zhang1, Yibo Hua1, Shouyong Liu1, Huiyu Dong1, Chao Zhang1, Shifeng Su1, Pu Li1, Chao Qin1 and Zengjun Wang1
1State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
2Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
*These authors contributed equally to this work
Correspondence to:
Zengjun Wang, email: [email protected]
Chao Qin, email: [email protected]
Keywords: CAPN2; renal cell carcinoma; metastasis/proliferation; EMT; AKT/mTOR signaling
Received: May 17, 2017 Accepted: October 11, 2017 Published: October 26, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 22083