Downregulation of Circular RNA circPSD3 Promotes Metastasis by Modulating FBXW7 Expression in Clear Cell Renal Cell Carcinoma

Xuexia Xie; Haomin Li; Chongqing Gao; Yiqi Lai; Junjie Liang; Zhiwei Chen; Zheng Chen; Baoli Heng; Nan Yao; Caiyong Lai

doi:10.1155/2022/5084631

Downregulation of Circular RNA circPSD3 Promotes Metastasis by Modulating FBXW7 Expression in Clear Cell Renal Cell Carcinoma

J Oncol. 2022 Mar 7:2022:5084631. doi: 10.1155/2022/5084631. eCollection 2022.

Authors

Xuexia Xie¹, Haomin Li¹, Chongqing Gao², Yiqi Lai³, Junjie Liang⁴, Zhiwei Chen⁴, Zheng Chen¹, Baoli Heng^{5

6

7}, Nan Yao², Caiyong Lai^{1

8

9}

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
² Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, China.
³ University of South China, Hengyang, China.
⁴ Department of Hepatological Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
⁵ Yingde Center, Institute of Kidney Surgery, Jinan University, Guangdong, China.
⁶ Department of Urology, People's Hospital of Yingde City, Yingde, China.
⁷ Postdoctoral Mobile Station, The First Clinical Medical College of Jinan University, Guangzhou, China.
⁸ Department of Urology, The Sixth Affiliated Hospital of Jinan University, Dongguan, China.
⁹ Yang Xi General Hospital People's Hospital, Yangjiang, China.

Abstract

Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been shown to play critical regulatory roles in clear cell renal cell carcinoma (ccRCC). Metastasis is the main contributor to the poor prognosis of patients with ccRCC. However, the role of circRNAs in ccRCC metastasis has not been fully elucidated. In this study, microarray and RNA-seq analyses revealed that circPSD3 (hsa_circ_0002111) was dramatically downregulated in ccRCC tissues compared to adjacent nontumor tissues. A qRT-PCR analysis performed on our ccRCC cohorts confirmed the downregulation of circPSD3 in ccRCC tissues and further suggested that a low level of circPSD3 expression was associated with tumor metastasis in patients with ccRCC. Based on the results of functional studies, circPSD3 significantly inhibited cell migration, invasion, and the epithelial-mesenchymal transition (EMT) in vitro and blocked pulmonary metastasis in vivo. Mechanistically, circPSD3 functioned as a competing endogenous RNA for microRNA 25-3p (miR-25-3p) to regulate F-box and WD repeat domain-containing 7 (FBXW7) expression. Further verification indicated that circPSD3 overexpression restrained an EMT-like phenotype in cells, while miR-25-3p partially rescued these effects. In summary, circPSD3 inhibits tumor metastasis by repressing the miR-25-3p/FBXW7-EMT axis and might be developed as a potential diagnostic and therapeutic target for ccRCC.