Open AccessKLK4 Silencing Inhibits the Growth of Chromophobe Renal Cell Carcinoma through ERK/AKT Signaling Pathway
Author(s) -
Fan Bo,
Niu Yunfeng,
Zhang Aili,
Wei Shufei,
Ma Yongliang,
Su Jianzhi,
Ren Zongtao
Publication year - 2022
Publication title -
kidney and blood pressure research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.806
H-Index - 51
eISSN - 1423-0143
pISSN - 1420-4096
DOI - 10.1159/000527412
Subject(s) - research article
Renal cell carcinoma (RCC) generally has a poor prognosis because of late diagnosis and metastasis. Despite its abundance in RCC cells, the functions of kallikrein-related peptidase 4 (KLK4) in RCC cells remain unknown. The results of this investigation were examined to discover if KLK4 gene silencing influences the development of RCC cells. Methods: The mRNA levels of KLK4 and the relationship between KLK4 and tumor stage in patients with RCC were analyzed from the GEPIA database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of KLK4. Cell Counting Kit 8 (CCK-8), colony formation, wound healing, and Transwell assays were used to examine the proliferation, invasion, and migration of RCC cells after KLK4 suppression. Finally, xenograft experiments in a mouse model helped understand the in vivo effects of KLK4 knockdown. Results: Our research found that KLK4 expression was upregulated in the kidney chromophobe (KICH) specimens and cell lines. Moreover, inhibiting KLK4 growth led to a slowdown in RCC cell proliferation and colony formation. Additionally, KLK4 knockdown inhibited migration, invasion, and epithelial-mesenchymal transition (EMT) of RCC cells. AKT and ERK phosphorylation were enhanced with KLK4 silencing. In the nude mouse xenograft cancer model, KLK4 silencing also prevented the expression of Ki-67, CD105, and the growth of tumors. Conclusion: KLK4 accelerated KICH progression via the ERK/AKT signaling pathway, providing a novel regulatory mechanism for KICH pathogenesis.