circ-LDLRAD3 Knockdown Reduces Cisplatin Chemoresistance and Inhibits the Development of Gastric Cancer with Cisplatin Resistance through miR-588 Enrichment-Mediated SOX5 Inhibition.

Background/Aims: Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). Methods: The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC50) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. Results: circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDLRAD3 knockdown decreased the IC50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. Conclusions: circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.

circ-NRIP1 Promotes Glycolysis and Tumor Progression by Regulating miR-186-5p/MYH9 Axis in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is a severe threat to human life, with high incidence and mortality. Circular RNAs (circRNAs) play crucial roles in the progression of GC. This study attempted to investigate the potential role of circ-NRIP1 and associated action mechanisms in GC cells. METHODS: The expression of circ-NRIP1 and miR-186-5p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, and migration were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry assay, and transwell assay, respectively. Cellular glycolysis, including cellular glucose uptake, lactate, and ATP/ADP ratios, was also detected by commercial assay kits. The protein levels of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) were quantified by Western blot. The relationship between miR-186-5p and circ-NRIP1 or myosin heavy chain 9 (MYH9) was predicted by the online bioinformatics tool, starBase, and verified by dual-luciferase reporter assay. Xenograft tumor model was used to evaluate biological function in vivo. RESULTS: The expression of circ-NRIP1 was up-regulated in tissues of GC patients and cells, as well as negatively associated with that of miR-186-5p in tissues. circ-NRIP1 knockdown inhibited cell proliferation, migration, and glycolysis, but induced apoptosis in HGC-27 and AGS cells. circ-NRIP1 competitively targeted miR-186-5p, and MYH9 was a target of miR-186-5p. miR-186-5p knockdown inverted the bio-function effects and glycolytic activation from circ-NRIP1 silencing in HGC-27 and AGS cells. Meanwhile, MYH9 overexpression could rescue the effects of miR-186-5p. Besides, miR-186-5p knockdown inverted the expression pattern of si-circ-NRIP1 transfection in GC cells. Additionally, in vivo experiments confirmed that sh-circ-NRIP1 inhibited tumor growth. CONCLUSION: circ-NRIP1 accelerated the glycolysis and GC progression by modulating MYH9 via miR-186-5p, suggesting that circ-NRIP1 was a promising biomarker for the treatment of GC.

Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance.

BACKGROUND: Esophageal carcinoma is a common kind of malignant tumor and about 90% of which is esophageal squamous cell carcinoma (ESCC), and it has a high incidence in China. In recent years it has been argued that angiogenesis plays a key role in tumor growth and metastasis and it is a complex process influenced by many factors. This study was aimed to investigate the expression of PC cell-derived growth factor (PCDGF or progranulin) and vascular endothelial growth factor (VEGF) in ESCC tissue and their relationship with clinical pathological parameters of ESCC, clarify the role of PCDGF and VEGF in the angiogenesis of ESCC. METHODS: The expression of PCDGF and VEGF in 50 surgical specimens from patients with ESCC and 20 with normal esophageal mucosa were detected by immunohistochemistry. The vascular endothelial cells in tumor tissues were labeled by antibody to CD105 for counting microvessel density (MVD). RESULTS: The expression of PCDGF and VEGF in ESCC was significantly higher than that in normal mucosa. Expression correlated with the depth of tumor invasion, lymph node metastasis, and TNM (classification tumor, nodes, metastasis). In ESCC, both the expression level of PCDGF and VEGF had a positive correlation with MVD and the expression of PCDGF had a significant correlation with the expression of VEGF. CONCLUSIONS: These results show that both of PCDGF and VEGE have higher expression in ESCC, which indicate that they have a close relationship with angiogenesis. They may be involved in tumor growth, infiltration and metastasis through promoting tumor angiogenesis and may be an important index reflecting biological behavior and prognosis of ESCC.