A‑kinase interacting protein 1 regulates the cell proliferation, invasion, migration and angiogenesis of clear cell renal cell carcinoma cells and affects the ERK/c‑Myc signaling pathway by binding to Rac1

Zhang,Yu; Zhang,Haijian; Han,Zhixing; Wang,Xudong; Li,Xuyu; Yuan,Pengfei; Ji,Shiqi; Liu,Qingjun

doi:10.3892/etm.2022.11489

A‑kinase interacting protein 1 regulates the cell proliferation, invasion, migration and angiogenesis of clear cell renal cell carcinoma cells and affects the ERK/c‑Myc signaling pathway by binding to Rac1

Authors:
- Yu Zhang
- Haijian Zhang
- Zhixing Han
- Xudong Wang
- Xuyu Li
- Pengfei Yuan
- Shiqi Ji
- Qingjun Liu
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Affiliations: Department of Urology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China, Department of Urology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
Published online on: July 5, 2022 https://doi.org/10.3892/etm.2022.11489
Article Number: 558
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A‑kinase interacting protein 1 (AKIP1) has previously been demonstrated to be overexpressed in clear cell renal cell carcinoma (ccRCC) tissues and is associated with patient prognosis. The aim of the present study was to explore whether AKIP1 can affect the proliferation, invasion, migration and angiogenesis of ccRCC cells via its interaction with Rac1. Furthermore, the influence of AKIP1 and therefore Rac1 on the expression of the downstream ERK/cellular (c)‑Myc signaling pathway was explored. The interaction between AKIP1 and Rac1 was determined using co‑immunoprecipitation. The mRNA and protein expression levels of AKIP1 and Rac1 in normal renal epithelial cell lines and ccRCC cell lines were detected using reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting, respectively. The transfection efficiency of small interfering RNA‑AKIP1 and the Rac1 overexpression vector were also confirmed using RT‑qPCR and western blotting. The viability, proliferation, invasion and migration of ccRCC cells following transfection were analyzed using the Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine staining, Transwell and wound healing assays, respectively. The tube formation ability of HUVECs was assessed using the tube formation assay. The protein expression levels of proliferation, invasion, migration and tube‑formation‑associated proteins as well as proteins associated with the ERK/c‑Myc signaling pathway, were detected via western blotting. The results demonstrated that AKIP1 expression levels were increased in ccRCC cell lines. AKIP1 knockdown inhibited the proliferation, invasion and migration of ccRCC cells and HUVEC tube‑formation. In addition, AKIP1 was demonstrated to bind to Rac1 in ccRCC cells and AKIP1 downregulation inhibited Rac1 expression. Furthermore, Rac1 overexpression reversed the effects of AKIP1 knockdown on ccRCC cells. AKIP1 knockdown also suppressed the ERK/c‑Myc signaling pathway, which was reversed by Rac1 overexpression. In conclusion, AKIP1 knockdown potentially suppressed the proliferation, invasion, migration and angiogenesis of ccRCC cells and inhibited the ERK/c‑Myc signaling pathway by binding to Rac1.

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