In Silico, In Vitro, and Clinical Investigations of Cathepsin B and Stefin A MRNA Expression and a Correlation Analysis in Kidney Cancer

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 May 14

PMID 35563761

Authors

Magdalena Rudzinska-Radecka

Anastasia S Frolova

Anastasia V Balakireva

Neonila V Gorokhovets

Vadim S Pokrovsky

Darina V Sokolova

Dmitry O Korolev

Natalia V Potoldykova

Andrey Z Vinarov

Alessandro Parodi

Andrey A Zamyatnin Jr

Affiliations

Soon will be listed here.

Abstract

The cysteine protease Cathepsin B (CtsB) plays a critical role in multiple signaling pathways, intracellular protein degradation, and processing. Endogenous inhibitors regulate its enzymatic activity, including stefins and other cystatins. Recent data proved that CtsB is implicated in tumor extracellular matrix remodeling, cell invasion, and metastasis: a misbalance between cathepsins and their natural inhibitors is often considered a sign of disease progression. In the present study, we investigated CtsB and stefin A (StfA) expression in renal cell carcinoma (RCC). mRNA analysis unveiled a significant and increase in RCC tissues compared to adjacent non-cancerogenic tissues and a higher CtsB expression in malignant tumors than in benign renal neoplasms. Further analysis highlighted a positive correlation between CtsB and StfA expression as a function of patient sex, age, tumor size, grade, lymph node invasion, metastasis occurrence, and survival. Alternative overexpression and silencing of CtsB and StfA confirmed the correlation expression between these proteins in human RCC-derived cells through protein analysis and fluorescent microscopy. Finally, the ectopic expression of CtsB and StfA increased RCC cell proliferation. Our data strongly indicated that CtsB and StfA expression play an important role in RCC development by mutually stimulating their expression in RCC progression.

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