Circular RNA (circRNA) can modulate the gene expression via sponging microRNA (miRNA) in multiple malignancies. Nevertheless, the detailed function of circ_0001658 in osteosarcoma (OS) and its regulatory mechanism remain elusive.Real-time PCR was carried out to detect the expressions of circ_0001658, miR-382-5p, and Y box-binding protein 1 (YB-1) mRNA in OS tissues. Besides, western blot was done to monitor YB-1 expression in OS cells. Chi-squared test was used to analyse the correlation between circ_0001658 and clinicopathologic characteristics of OS patients. CCK8 assay, colony formation assay, flow cytometry, and transwell assay were performed to determine the function of circ_0001658. Moreover, dualluciferase reporter gene assay was done to verify the targeting relationship between circ_0001658 and miR-382-5p. Compared with adjacent tissues, circ_0001658 displayed a significantly higher expression in OS tissues. Circ_0001658 could facilitate the proliferation, migration, and invasion of OS cells and impede apoptosis by sponging miR-382-5p. Further, circ_0001658 was proved to directly and negatively regulate the expression of miR-382-5 while positively modulate the expression of YB-1. Circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR-382-5p/YB-1 axis. Significance of the study:In recent years, the expression and function of circular RNA in cancer have been the focus of tumour research. The study on circular RNA helps elucidate the molecular pathology of tumorigenesis and cancer progression.This study demonstrated that circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR-382-5p/YB-1 axis. To our best knowledge, this work is the first to study the expression and function of circ_0001658 in cancer. K E Y W O R D Scirc_0001658, miR-382-5p, osteosarcoma, YB-1 | INTRODUCTIONOsteosarcoma (OS) is a common primary malignant bone tumour among children and adolescents, frequently diagnosed in the distal femur, the proximal tibia, and the proximal humerus. 1,2 Though multiple treatments offer symptomatic relief and modest improvement in survival for OS patients, the long-term disease-free survival rate of patients remains unfavourable, only 60% to 75%. 3,4 To make matters worse, the 5-year survival rate was only 27% to 55% in patients with local relapsing and distant metastasis treated by the available therapy clinically. 5 Hence, it is imperative to probe into the detailed mechanism of OS.Circular RNA (circRNA) is a novel class of endogenous noncoding RNA, which exists widely and stably in mammalian cells without the function of encoding proteins. 6,7 Circ-RNA, unlike linear RNAs, features a closed-loop structure. 8 This distinctive structure contributes

In previous years, progranulin (PGRN) has attracted increasing attention due to its oncogenic roles in several types of tumor. However, the clinical relevance of PGRN in gastric cancer remains to be elucidated. In the present study, 120 retrospective tissue samples were obtained from patients with primary gastric cancer, and the expression of PGRN was detected using immunohistochemistry. The results showed that 71 cases exhibited a high expression of PGRN, which was markedly higher than the 49 cases with a low expression of PGRN. Subsequent χ2 analysis confirmed for the first time, to the best of our knowledge, that a high level of PGRN was positively correlated with lymph node metastasis (P=0.048), lymphatic invasion (P=0.018) and advanced clinical stage (P=0.027). Survival analysis showed that PGRN was positively correlated with poorer overall survival (OS; P=0.0043) and progression‑free survival (PFS; P=0.0022). Univariate and multivariate Cox regression analysis showed that PGRN and clinical stage had a significant effect on the OS and PFS of the patients with gastric cancer. In addition, cell experiments confirmed that extracellular PGRN promoted the intracellular expression of PGRN in a concentration‑dependent manner in gastric cancer cells. The AKT and extracellular signal‑regulated kinase signaling pathways were involved in the upregulation of intracellular PGRN induced by extracellular PGRN in MKN‑45 and MGC‑803 gastric cancer cells. Taken together, the results of the present study suggested that PGRN may be important in the progression and prognosis of gastric cancer, and that the expression of PGRN was regulated in a positive feedback loop. These findings enhance current knowledge regarding PGRN in tumors.

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