In silico identification and targeting of key genes involved in renal cell carcinoma metastasis

Abstract

Metastasis is a challenge in the management of renal cell carcinoma (RCC). The clinical implications of RCC metastasis are significant, with patients experiencing a poorer response to treatment and a reduced life expectancy. Currently, there is no curative treatment for RCC metastasis, and systemic chemotherapy and immunotherapy remain mainstay therapies. However, emerging evidence suggests that targeted therapies may provide promising treatment options for improving the prognosis and quality of life of patients with metastatic RCC. The current study aimed to investigate the underlying molecular mechanisms of RCC metastasis and identify key therapeutic targets using computational approaches. Also, a library of FDA approved drugs was screened against the target genes to obtain potential inhibitors that can be used in therapies. Differential gene expression analysis followed by functional enrichment and protein-protein interaction analyses led to the identification of CCND2 and MMP9 as key genes involved in multiple process in the metastatic tumors in case of both clear cell and papillary cell renal carcinoma. Docking studies revealed good binding of drugs mysoline and ethisterone with CCND2 and canrenone and evodiamine with MMP9. Molecular Dynamics simulations showed stable and strong binding of these drugs with CCND2, but the identified drugs failed to have stable interactions with MMP9. Hence, our study reveals mysoline and ethisterone to be potential inhibitors that target CCND2 to control metastasis of RCC.