Biomedical Letters

Research article | https://doi.org/10.47262/BL/10.1.20230203

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

Abdul Jamil Khan 1, Islamuddin Khan 2, Shadman khan 3, Iman Qasim 4, Haroon Khan 5*

1 Biomedical Nano Center, School of Life Science, Inner Mongolia Agricultural University, Hohhot 010018, China

2 Complete Genomics Biochemistry-1, Department US CG Biochem. MGI Tech Co., Ltd. Beishan Industrial Zone, Yantian District, Shenzhen 518083, China

3 Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, School of Life Sciences, Inner Mongolia University, Hohhot 010020, China

4 Nishtar 2 Hospital, Multan Affiliated with University of Health Sciences, Lahore Pakistan

5 Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China

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.