ABSTRACT
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 (IC 50 ) 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-LDL-RAD3 knockdown decreased the IC 50 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.
ABSTRACT
Objective To investigate the relationships and clinicopathologic features of the expressions of cytochrome P450 2E1 (CYP2E1) and PC cell-derived growth factor (PCDGF) in esophageal squamous cell carcinoma (ESCC),and to determine the role of CYP2E1 and PCDGF in angiogenesis.Methods The expression levels of CYP2E1 and PCDGF in 42 surgical cancer specimens and 20 adjacent normal esophageal mucosa specimens from patients with ESCC were detected by immunohistochemistry.Results The positive expression rates of CYP2E1 and PCDGF in ESCC were 83.3 ％ (35/42) and 88.1％ (37/42),respectively,which were obviously higher than those of normal mucosa (P ＜ 0.05).Expression of PCDGF was correlated with the degree of histological differentiation (r =0.444,P ＜ 0.05),depth of tumor invasion (r =0.332,P ＜ 0.05),lymph node metastasis (r =0.476,P ＜ 0.05),and TNM classification (r =0.450,P ＜ 0.05).The expression of CYP2E1 was negatively correlated with tumor tissue differentiation (r =-0.518,P ＜ 0.05),and positively correlated with depth of invasion in ESCC (r =0.388,P ＜ 0.05).The expression of CYP2E1 was related to that of PCDGF in the tumor (r =0.483,P ＜ 0.05).Conclusion The expressions of CYP2E1 and PCDGF are synergistically involved in tumor growth,infiltration andmetastasis.Overexpression of CYP2E1 and PCDGF can be used as the important predictors for evaluating the biological behavior of ESCC and predicting prognosis of patients.
ABSTRACT
Objective To investigate the expression of PC cell-derived growth factor(PCDGF or progranulin)and vascular endothelial growth factor(VEGF)and the relationships between them and clinicopathologic features in esophageal squamous cell carcinoma(ESCC),helping to determine the role of PCDGF(progranulin)and VEGF in angiogenesis.Methods The expression of PCDGF(progranulin)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 tissue were labeled by antibody to CD105 for counting microvessel density(MVD).Results The expressions of PCDGF(progranulin)and VEGF in ESCC were obviously higher than normal mucosa.Their expression had positive correlation with depth of tumor invasion,lymph node metastasis,and TNM classification.In ESCC,both the expression level of PCDGF(progranulin)and VEGF had significant positive correlation with MVD and the expression of PCDGF had direct correlation with the expression of VEGF.Conclusion PCDGF marks tumor tissues with so high sensitivity that it can be a novel ESCC marker hopefully.The expression of both PCDGF(progranulin)and VEGF in ESCC has close relationship with angiogenesis,and they may take part in tumor growth,infiltration and metastasis through promoting tumor angiogenesis.