CircRNAs have emerged as potential therapeutic targets for diseases such as gastric cancer (GC). We identified highly dysregulated circRNAs in GC tissue and further explored their potential mechanisms in the progression of GC. Hsa_circ_0091994 (cicrRNA_105040) was identified as a highly upregulated circRNA in GC tissues, whose host gene is negatively associated with the overall survival of patients. Using cell counting kit-8 and Annexin V assays, we observed that hsa_circ_0091994 knockdown inhibited the viability of AGS and HGC-27 cells by inducing apoptosis. Scratch wound healing assays showed that hsa_circ_0091994 knockdown also inhibited GC cell healing. Bioinformatics analysis and a luciferase assays revealed that hsa_circ_0091994 knockdown inhibits GC progression by suppressing miR-324-5p and HMGA1 expression. The antitumor effect of hsa_circ_0091994 knockdown was confirmed in vivo using a mouse xenograft model. Hsa_circ_0091994 knockdown inhibited the progression of GC by inhibiting the miR-324-5p/HMGA1 axis.

Objective To investigate the expression and clinical significance of epithelial cell adhesion molecule(EpCAM) and Claudin-18 in gastric cancer.Methods Surgical specimens of gastric cancer were taken from 64 patients.The histological diagnostic criteria were based on WHO standards.Immunohistochemical staining was used to detect expression levels of EpCAM and Claudin-18 in all samples.The relationship between the expression of EpCAM and Claudin-18 and clinicopathological parameters of gastric cancer was analyzed.Correlations of the prognosis of gastric cancer patients with EpCAM and Claudin-18 expression were analyzed using the Cox proportional hazards regression model.Results The positive expression rate of EpCAM was elevated with the increase in tumor size and the occurrence of distant metastasis(x2 =4.526 and 36.090,P=0.033 and 0.000).There were significant differences in Claudin-18 protein expression among different age,TNM stage,growth pattern,depth of invasion and distant metastasis patients(all P＜0.05).Cox regression model analysis showed that tumor size and distant metastasis were the main risk factors affecting the survival of patients with gastric cancer (RR =50.076 and 1.617,P =0.016 and 0.032),while levels of EpCAM and Claudin-18 were not independent risk factors (both P ＞ 0.05).Conclusions EpCAM and Claudin-18 are closely related to the invasiveness of gastric cancer,but abnormally high levels of EpCAM and Claudin-18 are not independent risk factors for the prognosis of gastric cancer patients.

Objective To investigate the effect of miR-29c on radiosensitivity of hepatoma HepG2 cells by targeting AKT2 gene.Methods The expression of miR-29c in human normal hepatocytes THLE-3 and hepatoma cell HepG2 was detected by RT-PCR.The relationship between miR-29c and AKT2 were predicted by predicted by informative analysis and verified by dual luciferase reporter gene test and Western blot.miR-29c mimic/AKT2 gene recombinant plasmid and miR-29c inhibitor/ lentivirus vector AKT2 shRNA were transfected into HepG2 cells by Liposome 2000.The cells were irradiated with different doses (0,2,4,6 and 8 Gy) of X-rays,and the effects of miR-29/AKT2 on the survival and cell viability of HepG2 cells were detected by cloning and MTT assays.Results Compared with THLE-3 cells,the expression of miR-29c in HepG2 cells was significantly lower (t=17.816,P＜0.05).After 2,4,6 and 8 Gy X-ray irradiation,the survival of HepG2 cells was significantly lower than that of THLE-3 cells (t =4.541,6.823,7.218,9.363,P＜0.05),and the expression of miR-29c in HepG2 cells was significantly decreased (t =5.599,9.262,10.470,10.873,P＜0.05).The survival and viability of HepG2 cells were decreased by miR-29c overexpression (tsurvival rate =4.307,7.668,7.668,6.894,P＜0.05;tcell viability =3.443,8.116,13.434,P ＜ 0.05) but they were increased by miR-29c inhibition (tsurvival rate =4.003,6.713,7.141,P＜0.05;tcell viability =4.282,5.113,P＜0.05).Double luciferase reporter gene experiments showed that AKT2 was the target gene of miR-29c since the expression of AKT2 was negatively regulated by miR-29c.After the silence of AKT2 or overexpression of AKT2,the survival and viability of HepG2 cells were consistent with the overexpression of miR-29c or the inhibition of miR-29c,respectively.Conclusions MiR-29c increases the radiosensitivity of hepatoma cell HepG2 by targeting AKT2.

The aim of the present study was to investigate the correlation of STAT3 and AKT in HCC cells. HCC cells were transfected with si-STAT3 and si-AKT2 in vitro and the mRNA expression of STAT3 and AKT was detected by RT-PCR, and the protein expression was measured by western blot. MTT assays were used to evaluate cell proliferation, and Transwell assays were performed to detect the ability of migration and invasion. The relationship between STAT3 and AKT was analyzed by ChIP and Dual-luciferase reporter (DLR) assays. A nude mice experiment was used to verify the correlation. In the present study, we found that the expression of p-AKT2 and its downstream molecules were reduced in HCC cells transfected with si-STAT3, and the expression of p-STAT3 and its downstream molecules was decreased in HCC cells transfected with si-AKT2. Moreover, the ability of HCC cells proliferation, migration and invasion was decreased in si-STAT3 transfection group, but AKT2 reversed the role of si-STAT3 in HCC cells. The ChIP experiment found that STAT3 could bind to the AKT2 promoter in HCC cells. The DLR assay showed that the luciferase activity of AKT2 promoter was enhanced in HCC cells treated by IL-6. The nude mice experiment found that the tumor grew slowly after transfection with the STAT3-siRNA lentiviral vector, while AKT2 reversed the effect. STAT3 and AKT2 had mutual regulatory relationship, and STAT3 promoted the occurrence and development of HCC by regulating AKT2.