![]() Circ-CUX1 could directly bind EWSR1 and enhance its interaction with MAZ, leading to MAZ transactivation and neuroblastoma progression. For instance, circ-AMOTL1 was reported to be physically interacted with c-Myc, facilitating c-Myc nuclear translocation, resulting in upregulating a cohort of c-Myc targets. To date, only a small portion of researchers have focused on the direct interactions between circRNA and proteins. The most known sample is CDR1as, which harbors more than 70 conserved miR-7 binding sites. In this functional model, circRNA effectively sponges miRNAs to elevate their targets, indirectly regulating gene expression. The mechanisms by which circRNA works in cell fate are only beginning to be elucidated, and most researchers have focused on circRNA as a sponge of miRNA molecules. CircRNA is highly conservative and expressed in a tissue and developmental-stage specific pattern. With the advent of high-throughput sequencing, numerous circRNAs has been found and they are produced from special selective back splicing of pre-mRNA and are abundant in the eukaryotic cells. The classical RNA sequencing method can only separate RNA with characteristic “poly-A tail”, thus circRNA is discarded in the classical separation process due to the link between the head and tail, this is the reason why circRNA has long been ignored by scientists. Different from the traditional linear RNA, circRNA has a closed loop structure, which is not affected by RNA exonuclease, and is more stable and not easy to degrade. Therefore, dissecting mechanisms underlying HCC will yield new directions in clinical diagnosis and treatment for the benefit of patients.Ĭircular RNA (circRNA) is a new kind of special non coding RNA (ncRNA) molecule, which is the latest research hotspot in RNA field. And the prognosis of HCC is not optimistic, especially for patients with advanced clinical stage, when tumor spreads to the surrounding lymph nodes, the 5-year survival rate of patients is only 11% when cancer spreads to some important organs, the situation is worse, with a 5-year survival rate of only 3%. ![]() Although many patients are effectively diagnosed and treated in the early stage of the disease, the recurrence rate is still very high. Hepatocellular carcinoma (HCC) is the main histological subtype of primary liver cancer with rapidly increasing morbidity and mortality, especially in China. Our study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188–9, a specific STAT3 small-molecule inhibitor. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. ResultsĬirc-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Animal study was carried to test the role of circ-LRIG3 in vivo. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. GSEA software was applied to analyze the pathway related to circ-LRIG3. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. QRT-PCR and western blot were used to asses gene and protein expression, respectively. ![]() Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Circular RNA (circRNA) is emerging as an important player in human diseases, especially cancer.
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