Renal cell carcinoma (RCC) is the most common form of kidney cancer. Recent studies reported that Tescalcin was overexpressed in various tumor types. However, the status of Tescalcin protein expression in RCC and its biological function is uncertain. This study was designed to investigate the expression of Tescalcin in human RCC and its biological function.
shRNA transfection was performed to abrogates the expression of Tescalcin. Quantitative real time PCR and western blotting assays were used to determine mRNA and protein expression levels, respectively. The cell viability was analyzed by MTT and colony formation. Cell flow cytometry was used to assess pHi value and cell apoptosis. Cell invasive and migratory ability was measured with modified Boyden chamber assay. Xenograft model was setup to evaluate tumor growth.
Tescalcin was overexpressed in RCC tissues compared with matched normal tissues. It was also overexpressed in RCC cell lines relative that of normal cells. Suppression Tescalcin with specific shRNA resulted in the inhibition of cell proliferation, migration, invasion and apoptosis of RCC cells. Additionally, silencing of Tescalcin also caused the inhibition of the tumor growth in nude mice. Mechanistic study showed that Tescalcin regulated cell proliferation, migration and invasion via NHE1/pHi axis as well as AKT/NF-κB signaling pathway.
These findings demonstrate that atopic expression of Tescalcin facilitates the survival, migration and invasion of RCC cells via NHE1/pHi axis as well as AKT/ NF-κB signaling pathway, providing new perspectives for the future study of Tescalcin as a therapeutic target for RCC.
Experimental and molecular pathology. 2018 Dec 27 [Epub ahead of print]
Ai-Jing Luo, Jing Tan, Le-Ye He, Xian-Zhen Jiang, Zhi-Qiang Jiang, Qing Zeng, Kun Yao, Juan Xue
The Third Xiangya Hospital of Central South University, Key Laboratory of Medical Information Research (Central South University), College of Hunan Province, Changsha 410013, PR China; Department of Urology, the Third Xiangya Hospital of Central South University, Changsha 410013, PR China., Department of Urology, the Third Xiangya Hospital of Central South University, Changsha 410013, PR China., The Third Xiangya Hospital of Central South University, Key Laboratory of Medical Information Research (Central South University), College of Hunan Province, Changsha 410013, PR China; Department of Urology, the Third Xiangya Hospital of Central South University, Changsha 410013, PR China. Electronic address: .