EGR1 inhibits clear cell renal cell carcinoma proliferation and metastasis via the MAPK15 pathway.

Abstract

Background: Clear cell renal carcinoma (ccRCC), the leading histological subtype of RCC, lacks any targeted therapy options. Although some studies have shown that early growth response factor 1 (EGR1) has a significant role in cancer development and progression, its role and underlying mechanisms in ccRCC remain poorly understood.

Methods: The Cancer Genome Atlas (TCGA) database was utilized to examine the expression of EGR1 in ccRCC. The expression of EGR1 in 55 ccRCC tissues was evaluated using immunohistochemistry. The link between EGR1 expression and clinicopathological variables was examined through an analysis. Gain-of-function assays were employed to investigate EGR1's biological functions in ccRCC cells, involving proliferation, colony formation, invasion assays, and tumorigenesis in nude mice. In order to assess the protein expression of mitogen-activated protein kinase 15 (MAPK15), E-cadherin, matrix metalloproteinase-9/-2 (MMP-9 and MMP-2), Western blot technique was applied.

Results: The results revealed a decrease in EGR1 expression in ccRCC tissues. This decrease was strongly linked to TNM stage, lymphatic metastasis, tumor size, histological grade, and unfavorable prognosis in ccRCC patients. It has been demonstrated that overexpressing EGR1 inhibits the growth of xenograft tumors in vivo and inhibits cell colony formation, motility, and invasion in vitro. Furthermore, EGR1 can prevent the development and movement of ccRCC cells by controlling the expression of MMP-2, MMP-9, E-cadherin, and MAPK15.

Conclusions: The EGR1/MAPK15 axis may represent a promising target for drug development, with EGR1 serving as a possible target for ccRCC therapy.