CircUBAP2 Inhibits Proliferation and Metastasis of Clear Cell Renal Cell Carcinoma via Targeting miR-148a-3p/FOXK2 Pathway

Abstract

Clear cell renal cell carcinoma (ccRCC) is the prominent histological subtype of renal cell carcinoma (RCC) with high incidence of local recurrence and distant metastasis. It has been documented that circular ribonucleic acids (circRNAs) play crucial roles in the development of cancers; however, study on exploring the role of circRNAs in ccRCC still remains limited. In the present study, we aimed to evaluate the biological function of a novel circRNA UBAP2 (circUBAP2) in ccRCC and the underlying mechanism. Our results showed that circUBAP2 expression was significantly down-regulated in ccRCC tissues and cell lines. Overexpression of circUBAP2 significantly inhibited the proliferation, migration, and invasion of ccRCC cells. MiR-148a-3p was a target miRNA of circUBAP2 in ccRCC cells, and its expression levels in ccRCC tissues and cell lines were negatively correlated with circUBAP2 levels. Moreover, miR-148a-3p reversed the inhibitory effects of circUBAP2 on cell proliferation, migration, and invasion in ccRCC cells. Additionally, forkhead box K2 (FOXK2) was found to be a target gene of miR-148a-3p and regulated by miR-148a-3p in ccRCC cells. Furthermore, knockdown of FOXK2 reversed the inhibitory effects of miR-148a-3p inhibitor on ccRCC cells. In conclusion, these findings indicated that circUBAP2 functioned as a novel tumor suppressor in ccRCC through regulating the miR-148a-3p/FOXK2 axis. Therefore, circUBAP2 might serve as a potential therapeutic target for the treatment of ccRCC.

Functions of circular RNAs in bladder, prostate and renal cell cancer (Review)

“…2 ) ( 56 ). FOXK2 was found to translocate to the nucleus, be dependent on the AKT-mTOR signaling pathway, be expressed at a low level in ccRCC, and impair tumor cell proliferation and metastasis; however, its effect could be enhanced by circ_0001846 or attenuated by miR-148a-3p ( 57 ).…”

Circular RNAs as Prognostic Biomarkers in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

“…In addition to its oncogenic role, Chen et al (2019 ) also found that circular RNA hsa-circ-0072309 can play an antitumor role by deactivating the PI3K/AKT and mTOR pathways by sponging miR-100. Sun et al (2020 ) found that circUBAP2 can regulate the miR-148a-3p/FOXK2 pathway to inhibit the proliferation and metastasis of RCC. Furthermore, circRNAs can also regulate transcription factors to impact tumor initiation and evolution.…”

Use of Circular RNAs in Diagnosis, Prognosis and Therapeutics of Renal Cell Carcinoma

“…In fact, Sun et al demonstrated that the overexpression of circ-UBAP2 inhibited the proliferation, migration, and invasion of ccRCC cells. Regarding the molecular mechanisms, it was found that circ-UBAP sponges miR-148a-3p, which in turn regulates the expression levels of the FOXK2 gene ( Sun et al, 2020b ). Therefore, in brief, circ-UBAP2 works as a tumor suppressor in ccRCC through regulation of the miR-148a-3p/ FOXK2 axis.…”