Circular RNA-ZFR Inhibited Cell Proliferation and Promoted Apoptosis in Gastric Cancer by Sponging miR-130a/miR-107 and Modulating PTEN

Abstract

PurposeThis study aimed to probe into the associations among circular RNA ZFR (circ-ZFR), miR-130a/miR-107, and PTEN, and to investigate the regulatory mechanism of circ-ZFR‒miR-130a/miR-107‒PTEN axis in gastric cancer (GC).Materials and MethodsGSE89143 microarray data used in the study were acquired from publicly available Gene Expression Omnibus database to identify differentially expressed circular RNAs inGC tissues. The expressions of circ-ZFR, miR-130a, miR-107, and PTEN were examined by real-time reverse transcription polymerase chain reaction, while PTEN protein expression was measured by western blot. The variation of GC cell proliferation and apoptosis was confirmed by cell counting kit-8 assay and flow cytometry analysis. The targeted relationships among circZFR, miR-130a/miR-107, and PTEN were predicted via bioinformatics analysis and demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation assay. The impact of ZFR on gastric tumor was further verified in xenograft mice model experiment.ResultsCirc-ZFR and PTEN were low-expressed whereas miR-107 and miR-130a were highexpressed in GC tissues and cells. There existed targeted relationships and interactions between miR-130a/miR-107 and ZFR/PTEN. Circ-ZFR inhibited GC cell propagation, cell cycle and promoted apoptosis by sponging miR-107/miR-130a, while miR-107/miR-130a promoted GC cell propagation and impeded apoptosis through targeting PTEN. Circ-ZFR inhibited cell proliferation and facilitated apoptosis in GC by sponging miR-130a/miR-107 and modulating PTEN. Circ-ZFR curbed GC tumor growth and affected p53 protein expression in vivo.ConclusionCirc-ZFR restrained GC cell proliferation, induced cell cycle arrest and promoted apoptosis by sponging miR-130a/miR-107 and regulating PTEN.

Circular RNA hsa_circ_0008344 regulates glioblastoma cell proliferation, migration, invasion, and apoptosis

“…Therefore, the carcinogenic mechanisms driven by circRNAs may occur through their interaction with miRNAs on regulating gene expression. Increased evidence has confirmed this idea that circular RNA‐ZFR inhibited cell proliferation and promoted apoptosis in gastric cancer by sponging miR‐130a/miR‐107 and modulating PTEN, circ‐ITCH inhibited bladder cancer progression by sponging miR‐17/miR‐224 and regulating p21 and PTEN expression, and hsa_circ_0046701 promoted carcinogenesis by increasing the expression of miR‐142‐3p target ITGB8 in glioma . Furthermore, hsa_circ_0008344 may bind to several miRNAs, such as miR‐433‐3p and miR‐450b‐3p, predicted by bioinformatics, while miR‐433‐3p has been found to suppress cell growth and enhance chemosensitivity by targeting CREB in glioblastoma .…”

The Regulatory Functions of Circular RNAs in Digestive System Cancers

“…In addition, miR-630 could obstruct the function of circRNA_100269 [42]. Circ-ZFR induced cell cycle arrest, suppressed GC cell proliferation, and promoted apoptosis through sponging miR-107/miR-130a and adjusting PTEN, and circ-ZFR regulated the expression level of p53 protein in vivo [43].…”

“…High-throughput RNA sequencing is suitable for identifying new circRNAs and splice sites of circRNAs with sufficient underlying sequencing depth. Total RNA was treated with RNase R to degrade the linear RNA in library construction for screening circRNAs [43]. Then, circRNAs were experimentally validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) with GAPDH as the reference gene [43].…”

“…Total RNA was treated with RNase R to degrade the linear RNA in library construction for screening circRNAs [43]. Then, circRNAs were experimentally validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) with GAPDH as the reference gene [43]. Covalent loci of circRNA can be verified through Sanger sequencing.…”

<p>The Down-Regulation of lncRNA PCAT18 Promotes the Progression of Gastric Cancer via MiR-107/PTEN/PI3K/AKT Signaling Pathway</p>

“…13 In addition, the down-regulation of miR-107 inhibits GC cell growth, promotes cell cycle arrest and apoptosis through regulating PTEN. 14 MiR-107 also induces GC cell growth by targeting FOXO1. 15 However, the role of miR-107 reported in GC researches still remains controversial, for example, one study also reported that miR-107 inversely inhibits GC progress by targeting PI3K/AKT pathway, and therefore functions as a tumor suppressor.…”