CircPCNXL2 sponges miR-153 to promote the proliferation and invasion of renal cancer cells through upregulating ZEB2

Abstract

Increasing evidence showed that circular RNAs (circRNAs) play critical roles in tumorigenesis. However, the roles and underlying mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) remain unclear. In the present study, we identified a novel circRNA circPCNXL2, which was significantly upregulated in ccRCC by circular RNA microarray. Further analysis revealed that circPCNXL2 was significantly increased and correlated with poor overall survival of ccRCC patients. Function assays revealed that circPCNXL2 knockdown reduced RCC cells proliferation, invasion in vitro, and decreased tumor growth in vivo. In mechanism study, we showed that circPCNXL2 could be bind to miR-153 as a miRNA sponge to regulate ZEB2 expression in RCC progression. In addition, our data reported that the effects of circPCNXL2 inhibition on RCC cells proliferation and invasion could be abolished by miR-153 inhibitors. Altogether, we demonstrated that circPCNXL2 could regulate RCC cells proliferation and invasion by miR-153/ZEB2 axis, suggesting circPCNXL2 might serve as a potential therapeutic target for ccRCC treatment.

Circular RNA hsa_circ_001895 serves as a sponge of microRNA‐296‐5p to promote clear cell renal cell carcinoma progression by regulating SOX12

“…CircRNAZNF609 promoted cell progression of ccRCC by sponging miR‐138‐5p targeted forkhead box P4 . CircPCNXL2 promoted cell progression of ccRCC by sponging miR‐153 Zinc finger E‐box‐binding homeobox 2 . Therefore, circRNAs, considered potential prognosis biomarkers of ccRCC, may not only contribute to early diagnosis, but also improve the individualized treatment of ccRCC patients …”

Noncoding RNAs and Its Implication as Biomarkers in Renal Cell Carcinoma: A Systematic Analysis

“…Another, novel circRNA, circPCNXL2 was significantly upregulated in renal cancer. Indeed high abundance of circPCNXL2 was directly linked with poor survival rate of RCC patients [50]. Knockdown of circPCNXL2 has shown to reduceRCC cell proliferation in invitro and in vivo studies.…”

“…Mechanistically, circATP2B1 acts as miRNA sponge of miR-204-3p and influence the expression of estrogen receptor beta (ERβ), together they influence RCC progression, suggesting circRNA ATP2B1 as prognostic biomarker for renal disease [51]. The Fibroblast growth factor receptor-like 1 expression of circPCNXL2 was significantly increased in RCC patients, indeed the higher expression corresponds to poor survival of ccRCC patients [50]. Quantitative expression analysis of A-498, AXHN, ACHN, OS-RC-2, 769-P and G-401 as numerous renal cell lines showed increased expression of circ-ZNF609 [55].…”

Overexpression of antisense long non‑coding RNA ZNF710‑AS1‑202 promotes cell proliferation and inhibits apoptosis of clear cell renal cell carcinoma via regulation of ZNF710 expression

“…renal cell carcinoma (rcc), which originates from renal parenchyma urinary tubular epithelial cells, is one of the most common malignant tumors of the urinary system (1)(2)(3). clear cell rcc (ccrcc) accounts for ~80% of all rcc cases (1,(3)(4)(5)(6).…”