<p>circZNF609 promotes the proliferation and migration of gastric cancer by sponging miR-483-3p and regulating CDK6</p>

Abstract

ObjectiveTo explore the regulatory effects of circZNF609 on proliferative and migratory capacities of gastric cancer (GC) and its underlying mechanism.MethodsExpression level of circZNF609, CDK6 and miR-483-3p in GC tissues and cells were detected qRT-PCR verification. CCK-8 and transwell assay were conducted the cell viability and migratory capacities of GC cells. Dual luciferase assay was enrolled to confirm the interaction among circZNF609, CDK6 and miR-483-3p. Western blot was used to detect the protein level of CDK6.ResultsExpression levels of circZNF609 were higher in GC patients by qRT-PCR.GC patients with higher expression of circZNF609 were expected to have a higher TNM stage and lower 5-year survival than those with lower expression. ROC curves showed a well diagnostic value of circZNF609 in GC. Treatment of RNase R in GC cells downregulated the expression of ZNF609, whereas circZNF609 expression did not change. Furthermore, cytoplasmic expression of circZNF609 was higher than those of nuclear expression. Besides, biological experiments indicated that overexpression of circZNF609 promoted the proliferative and migratory capacities of GC cells. To demonstrate the underlying mechanism of circZNF609, we found that circZNF609 bound to miR-483-3p, which presented a lower expression in GC tissues than that of paracancerous tissues. Both circZNF609 and miR-483-3p could bind to Ago2, suggesting that circZNF609 may act as a sponge of miR-483-3p. In addition, the effect of overexpressed circZNF609 on cellular behaviors of GC cells were partly reversed by overexpression of miR-483-3p. Bioinformatics suggested that CDK6 has a potential binding site with miR-483-3p. The expression of CDK6 markedly increased in GC tissues and cells, which was negatively correlated with miR-483-3p expression. Dual-luciferase reporter gene results indicated that miR-483-3p could bind to the 3’-UTR of CDK6. Moreover, miR-483-3p downregulated CDK6 at both mRNA and protein levels. Overexpression of miR-483-3p inhibited proliferative and migratory capacities of GC cells, which were reversed by CDK6 overexpression.ConclusionIn summary, the expression of circZNF609 is upregulated in GC. CircZNF609 can be used as the sponge of miR-483-3p to regulate the expression level of CDK6, thus participating in the progression of GC by regulating the proliferative and migratory capacities of GC cells.

<p>Circular RNA ZNF609 Promoted Hepatocellular Carcinoma Progression by Upregulating PAP2C Expression via Sponging miR-342-3p</p>

“…22 CircZNF609 enhanced gastric cancer migration and invasion through modulating CDK6 via sponging miR-483-3p. 23 In this study, we predicted miRNA targets of circZNF609 by CircBank informatic tool. Among the potential targets, we chose miR-342-3p for further study due to its anti-tumor features reported previously.…”

Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity

“…Because circZNF609 has been reported to work as a competing endogenous RNA for many miRNAs ( He et al., 2020 ; Jin et al., 2019 ; Zhu et al., 2019 ; Liu et al., 2021 ; Wang et al., 2018 ; Wu et al., 2019 ; Liu et al., 2019 ), we checked whether the modulation of CKAP5 mRNA by circZNF609 could be mediated by some miRNAs targeting both transcripts. We found no significant shared binding sites of microRNAs expressed in RD cells among circZNF609 and CKAP5 mRNA ( Figure S4 C), ruling out an miRNA-mediated effect.…”

“…In this work, we studied circRNA zinc finger protein 609 (circZNF609), a circRNA previously described to be regulated and to control human primary myoblast and embryonal rhabdomyosarcoma (ERMS) cell proliferation ( Legnini et al., 2017 ; Rossi et al., 2019 ; di Timoteo et al., 2020 ). CircZNF609 was found to also be upregulated in several types of human cancers, such as prostate cancer ( Jin et al., 2019 ), breast cancer ( Wang et al., 2018 ), gastric cancer ( Wu et al., 2019 ; Liu et al., 2019 ), nasopharyngeal carcinoma ( Zhu et al., 2019 ; Liu et al., 2021 ), and hepatocellular carcinoma ( He et al., 2020 ), where its depletion has been linked with reduced aggressiveness of tumor cells. Although those studies pointed to circZNF609 as an miRNA sponge, we significantly advanced our understanding of the molecular mechanism through which it affects cell proliferation by focusing on its interactions with mRNAs.…”

The prognostic value of circRNAs for gastric cancer: A systematic review and meta‐analysis

“…Forty‐three articles including non‐data studies, non‐prognosis studies, nonhuman studies, and noncompliant studies were excluded through intensive reading of the full text. Finally, 35 literature studies with a total of 3135 patients were included in this meta‐analysis 8,10,12–44 . The process is shown in Figure 1.…”