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Circ-ITCH, a novel circRNA, was generated from several exons of itchy E3 ubiquitin protein ligase (ITCH). Recently, circ-ITCH has been demonstrated to be involved in cancer development. However, there have been few investigations on the specific role of circ-ITCH in glioma. In this study, we performed quantitative real-time polymerase chain reaction analysis and identified that circ-ITCH was significantly downregulated in glioma tissues and cell lines. The function assays showed that upregulation of circ-ITCH inhibited glioma cell proliferation and invasion in vitro as well as reduced cell growth in vivo. Moreover, miR-106a-5p was found serving as a target of circ-ITCH and miR-106a-5p mimics could reverse the inhibitory effect of circ-ITCH on glioma cell proliferation and invasion. We also revealed that circ-ITCH increased SASH1 expression by sponging miR-106a-5p in glioma cells. In addition, SASH1 downregulation could abrogate the suppressive effect of circ-ITCH on glioma progression. Taken together, our results suggested that circ-ITCH could suppress glioma cell proliferation and invasion via regulating the miR-106a-5p/SASH1 axis, elucidating a novel molecular target for glioma treatment.

MafF is a member of the basic leucine zipper (bZIP) transcription factor Maf family and is commonly downregulated in multiple cancers. But the expression and function of MafF in hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the relationship between endogenous MafF expression and HCC progression and explored the regulatory mechanism of MafF expression in HCC. We found that MafF decreased in HCC tissues and cells. Lentivirus-mediated MafF overexpression inhibited HCC cell proliferation and induced cell apoptosis. Bioinformatics analysis and luciferase assay identified MafF as a direct target of miR-224-5p. RNA pull-down assay demonstrated that circular RNA circ-ITCH could sponge miR-224-5p specifically in HCC. The rescue experiments further elucidated that the expression and antitumor effects of MafF could be regulated via the circ-ITCH/miR-224-5p axis. This study verified that MafF acted as a tumor suppressor in HCC and revealed the upstream regulation mechanism of MafF, which provided a new perspective for potential therapeutic targets of HCC.

Background This study was to investigate the correlation of circ-ITCH expression with tumor features, disease free survival (DFS) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients, and the effect of its dysregulation on cells proliferation and apoptosis of NSCLC cells. Methods Tumor tissue and paired adjacent normal tissue samples from 190 surgical NSCLC patients were collected and used for detecting circ-ITCH expression by qPCR. Circ-ITCH expression was also measured in normal pulmonary epithelial cell line and 4 NSCLC cell lines by qPCR. Patients’ baseline characteristics were recorded and DFS as well as OS were calculated. Blank, circ-ITCH overexpression, blank shRNA, circ-ITCH shRNA plasmids were transferred into NSCLC cell line (A549 cells) as NC(+), Circ-ITCH(+), NC(−) and Circ-ITCH(−) groups. Cells proliferation was measured using CCK-8 and cells apoptosis rate was measured using annexin V (AV)/propidium iodide (PI). Results Circ-ITCH expression was decreased in tumor tissue compared with paired adjacent tissue, and was negatively correlated with tumor size, lymph node metastasis and TNM stage. And circ-ITCH high expression was associated with favorable DFS and OS. In vitro experiments revealed that compared with normal pulmonary epithelial cell line BEAS-2B, circ-ITCH expression was reduced in NSCLC cell lines HCC827, A549, NCI-H1299 and NCI-H460. And cells proliferation was decreased in Circ-ITCH(+) group and elevated in Circ-ITCH(−) group at 72 h. Cells apoptosis rate was increased in Circ-ITCH(+) group and decreased in Circ-ITCH(−) group at 72 h. Conclusions Circ-ITCH associates with less advanced tumor features and prolonged survival, and it inhibits cells proliferation while promotes cells apoptosis in NSCLC.