CircRTN4 inhibits the progression of gastric cancer by sponging miR-424-5p and regulating LATS2 expression

Abstract

Purpose: To determine the expression of circRTN4 in gastric cancer (GC) and its role in tumor progression.
 Methods: GEO dataset GSE93541 was analyzed using GEO2R. Starbase website was used to predict the combination of miRNA and circRTN4. The relationship between circRTN4 and prognosis was analyzed using Kaplan-Meier Plotter database, while expression levels of circRTN4, miR-424-5p, and LATS2 were assessed by quantitative real time-polymerase chain reaction (qRT-PCR). CCK8, EDU, Transwell, and Western blot were used to assess GC proliferation, migration, invasion, and stemness. Lastly, co-transfection of miR-424-5p or si-LAST2 was reversely used to demonstrate the regulatory effect of circRTN4 on the progression of gastric cancer cells. Significantly downregulated circRTN4 in GC was screened, and the combined miR-424-5p and downstream gene LATS2 were predicted by Starbase.
 Results: The average relative expression of circRTN4 mRNA in GC tissues was significantly lower than in adjacent tissues. MiR-424-5p was highly expressed in tumor tissues, while LATS2 decreased (p < 0.05). Low expression of circRTN4 was associated with a low survival rate in patients. pLCDH- circRTN4 significantly inhibited the proliferation of gastric cancer cells (p < 0.05). Overexpression of circRTN4 inhibited the migration and invasion of tumor cells, while pLCDH-circRTN4 reduced the ability of GC stem cells and expressions of MMP2 and OCT4.
 Conclusion: Expression of circRTN4 decreases in GC, and contributes to the development and progression of this disease by increasing the levels of LATS2 and binding with miR-424-5p. This suggests that circRTN4 may serve as a promising prognostic marker as well as a potential therapeutic target for gastric cancer

CircPDSS1 accelerates malignant progression of renal cell carcinoma through sponging of miR-182-5p

“…CircRNAs present a structure of a covalently closed loop by joining the 5' and 3' terminals [12,13]. As ceRNAs, circRNAs exert an interactive relationship with miRNAs, lncRNAs and proteins [15][16][17], due to their specificity, stability and abundance, circRNAs are utilized as biological hallmarks [18,19].…”

“…Identification of specifically expressed genes during the progression of RCC may guide novel treatment in clinical practice [11]. CircRNAs are endogenous RNAs reversely spliced through gene transcription and posttranscriptional regulation, thus participating in cell physiology and disease processes [12,13]. They were initially discovered in viruses and considered to be produced by wrong splicing of gene sequences [13,14].…”

“…CircRNAs are endogenous RNAs reversely spliced through gene transcription and posttranscriptional regulation, thus participating in cell physiology and disease processes [12,13]. They were initially discovered in viruses and considered to be produced by wrong splicing of gene sequences [13,14]. With the development of high-throughput sequencing and bioinformatics analyses, a great number of circRNAs have been identified in bacteria, plants and animals [14,15].…”

“…Some circRNAs are able to translate proteins [16,17]. Importantly, circRNAs are featured by tissue and cell specificities [13][14][15]. It is believed that circRNAs serve as prognostic and therapeutic hallmarks for tumor diseases [18,19].…”