circ-ITCH Expression Research Articles

Circular RNA ITCH suppresses proliferation and promotes apoptosis in human epithelial ovarian cancer cells by sponging miR-10a-α.

To explore the effect of Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) on regulating epithelial ovarian cancer (EOC) cells proliferation and apoptosis, as well as its potential target microRNAs (miR) in vitro. Circ-ITCH mimic, blank mimic, Circ-ITCH inhibitor and blank inhibitor plasmids were transfected into SKOV3 cells. Rescue experiments were carried out by transfecting blank mimic, miR-10a mimic, Circ-ITCH mimic and miR-10a mimic/Circ-ITCH mimic plasmids into SKOV3 cells. Quantitative polymerase chain reaction (qPCR) was performed to detect RNA expression. Cells proliferation was determined by Cell Counting Kit-8 (CCK-8) assay, and cells apoptosis rate was detected using Annexin V (AV) / propidium iodide (PI) assay. Circ-ITCH expression was decreased in Human EOC cell lines SKOV3, A-2780, OVCAR-3 and HO-8910 compared with human normal ovarian epithelial cell line IOSE80, and the most significant reduction of Circ-ITCH expression was presented in SKOV3 cells. Cells proliferation was suppressed by Circ-ITCH mimic transfection and promoted by Circ-ITCH inhibitor transfection in SKOV3 cells. Cells apoptosis was enhanced by Circ-ITCH mimic transfection and inhibited by Circ-ITCH inhibitor transfection in SKOV3 cells. In addition, Circ-ITCH adversely regulated miR-10a expression in SKOV3 cells but not miR-4251 or miR-6505. Rescue experiments were subsequently performed, which exhibited that Circ-ITCH adversely regulated miR-10a expression, whereas miR-10a did not affect Circ-ITCH expression. And most importantly, miR-10a mimic attenuated the effect of Circ-ITCH on reducing proliferation and promoting apoptosis in SKOV3 cells. Circ-ITCH suppresses cells proliferation and promotes cells apoptosis via sponging miR-10a in EOC cells.

Circular RNA circ-ITCH inhibits bladder cancer progression by sponging miR-17/miR-224 and regulating p21, PTEN expression

BackgroundCirc-ITCH is a circRNA generated from several exons of itchy E3 ubiquitin protein ligase (ITCH) and tumor suppressor served as a sponge for certain miRNAs targeting their parental transcripts of ITCH. However, the role of circ-ITCH in bladder cancer (BCa) was not reported. In the present study, we investigated the role of circ-ITCH in BCa.MethodsQuantitative real-time PCR was used to detect the expression of circ-ITCH and survival analysis was adopted to explore the association between circ-ITCH expression and the prognosis of BCa. BCa cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion, cell cycle and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effect of circ-ITCH in BCa. Biotin-coupled probe pull down assay, Biotin-coupled miRNA capture, Fluorescence in situ hybridization and Luciferase reporter assay were conducted to confirm the relationship between the circ-ITCH and the microRNA.ResultsIn the present study, we found that circ-ITCH, is down-regulated in BCa tissues and cell lines. BCa patients with low circ-ITCH expression had shortened survival. Enforced- expression of circ-ITCH inhibited cells proliferation, migration, invasion and metastasis both in vitro and in vivo. Mechanistically, we demonstrated that circ-ITCH up-regulates the expression of miR-17 and miR-224 target gene p21 and PTEN through ‘sponging’ miR-17 and miR-224, which suppressed the aggressive biological behaviors of BCa.Conclusionscirc-ITCH acts as a tumor suppressor by a novel circ-ITCH/miR-17, miR-224/p21, PTEN axis, which may provide a potential biomarker and therapeutic target for the management of BCa.

Polymorphisms and expression pattern of circular RNA circ-ITCH contributes to the carcinogenesis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) ranks the sixth most common cancer and the third cause of cancer-related mortality worldwide. Recent studies identified that circ-ITCH Suppresses mutiple cancers proliferation via inhibiting the Wnt/beta-Catenin pathway. In current study, conducted a genetic association study together with epidemiological follow-up study to delineate the role of circ-ITCH in the development and progression of HCC. we found rs10485505 (adjusted OR =1.18; 95% CI=1.06-1.31; P value =3.1×10-3) and rs4911154 (adjusted OR =1.27; 95% CI=1.14-1.43; P value =3.7×10-5) were significantly associated with increased HCC risk. The expression level of circ-ITCH was significantly lower in HCC tissues, compared with that in adjacent tissues (P value < 0.001). Cox regression analysis indicated that high expression of circ-ITCH was associated with favorable survival of HCC (HR=0.45; 95% CI=0.29-0.68; P value < 0.001). These results indicate that circ-ITCH may have an inhibitory effect on HCC, and could serve as susceptibility and prognostic biomarkers for HCC patients.