No abstract

This study aimed to determine the correlation between HIF-1α and miR-27a expression and to evaluate the effect of inhibition of HIF-1α expression on miR-27a expression and drug resistance in gastric cancer (GC). In the present study, real time-PCR and Western blot were performed to detect the expression of HIF-1α in GC tissues and cell lines. Then, OCUM-2MD3/L-OHP cells were transfected with HIF-1α-siRNA, a miR-27a mimic or pcDNA-HIF-1α, and cell survival was determined via the MTT assay. The expression of HIF-1α, miR-27a, and MDR-related genes was measured via real time-PCR and Western blot. ChIP and dual luciferase activity assays were performed to assess the transcriptional regulation of HIF-1α and miR-27a. The results revealed that transfection with HIF-1α-siRNA markedly decreased the levels of miR-27a, resulting in dramatically enhanced inhibition of the proliferation rate of OCUM-2MD3/L-OHP cells. Compared to non-transfected cells, the survival rate was significantly reduced in the cells transfected with HIF-1α-siRNA after treatment with L-OHP. The cell survival rate was significantly increased in OCUM-2MD3/L-OHP cells transfected with the miR-27a mimic, whereas HIF-1α overexpression did not result in any clear change in cell survival. The results of the dual luciferase activity assay demonstrated that HIF-1α enhances the transcriptional activity of the miR27a promoter in cells transfected with a reporter plasmid containing the upstream promoter region of miR27a together with pcDNA-HIF-1α. ChIP analysis suggested that HIF-1α directly binds to the promoter region of miR27a. Inhibition of HIF-1α or miR27a expression decreased MDR1/P-gp, LRP, and Bcl-2 expression in OCUM-2MD3/L-OHP cells. Thus, we found that HIF-1α is closely associated with MDR in GC and that HIF-1α may suppress MDR1/P-gp, LRP and Bcl-2 expression by inhibiting miR-27a expression.

Background: Robotic-assisted gastrectomy has been used for treating gastric cancer since 2002. This meta-analysis was conducted to systematically evaluate the efficacy of Da Vinci robotic distal subtotal gastrectomy (RDG) or laparoscopic distal subtotal gastrectomy (LDG) in patients with gastric cancer. Methods: We conducted searches in domestic and foreign databases, and collected literature in Chinese and English on the efficacy of RDG and LDG for gastric cancer that have been published since the inception of the database. RevMan 5.4.1 was used for meta-analysis and drawing and Stata14.0 was used for publication bias analysis. Results: A total of 3293 patients in 15 studies were included, including 1193 patients in the RDG group and 2100 patients in the LDG groups respectively. The meta-analysis showed that intraoperative blood loss was significantly lower and the number of resected lymph nodes was higher in the RDG group compared to that in the LDG group. In addition, the times to first postoperative food intake and postoperative hospital stay were shortened, and there was a longer length of distal resection margin and prolonged duration of operation. No significant differences were found between the 2 groups with respect to the first postoperative anal exhaust time, length of proximal resection margin, total postoperative complication rate, postoperative anastomotic leakage rate, incidence of postoperative gastric emptying disorder, pancreatic fistula rate, recurrence rate, and mortality rate. Conclusion: RDG is a safe and feasible treatment option for gastric cancer, and it is non-inferior or even superior to LDG with respect to therapeutic efficacy and radical treatment.

Formononetin (Form), a phytoestrogen extracted from the roots of Astragalus membranaceus, is one of the fundamental herbs used in traditional Chinese medicine because of its protective effects against certain malignant tumors. However, its role in colon carcinoma cells and the underlying molecular mechanisms have not been completely elucidated. The present study aimed to demonstrate that Form significantly inhibited the proliferation and invasion of the colon carcinoma cell lines SW1116 and HCT116. Mechanistic studies have suggested that Form suppresses colon carcinoma cell growth by downregulating cell cycle-associated protein (cyclin D1) expression and arresting the cell cycle at the G0-G1 checkpoint. Further studies revealed that treatment with Form inhibits matrix metalloproteinase (MMP)2 and MMP9 expression. Aditionally, the results demonstrated that Form significantly increased microRNA (miR)-149 expression. Following miR-149 overexpression in SW1116 and HCT116 cells using an miR-149 mimic, cell viability and Ephrin type-B receptor 3 (EphB3) levels decreased. Furthermore, the inhibitory effects of Form were associated with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. These results indicated the suppressive effect of Form on colon carcinoma cell proliferation and invasion, possibly via miR-149-induced EphB3 downregulation and the inhibition of the PI3K/AKT and STAT3 signaling pathways. Overall, Form may be used as a novel candidate for the clinical treatment of colorectal cancer in the future.

Emerging evidence indicates that microRNAs are involved in the development and progression of gastric cancer (GC), functioning as tumor suppressors or oncogenes. The aim of the current study was to explore the potential mechanism of microRNA-425-5p (miR-425-5p) in GC. Using reverse transcription quantitative polymerase chain reaction, miR-425-5p expression was detected in GC cell lines (SGC-7901, MKN-28, MKN-45, BGC-823 and AGS) and the GES-1 cell line. Cell proliferation, soft agar colony formation, flow cytometry, haptotactic migration and matrigel chemoinvasion assays were used to test the proliferation, apoptosis, invasion and migration of BGC-823 cells transfected with miR-425-5p mimics or an inhibitor. Female BALB/c mice were randomly divided into three groups. Each experimental group contained five mice. BGC 823 cells were stably transfected with miR-425-5p inhibitor, wild type or negative control and were injected into the mice through the tail vein. It was found that miR-425-5p expression was significantly upregulated in all the GC cell lines when compared with the GES-1 cell line. Downregulation of miR-425-5p expression inhibited GC cell proliferation, invasion and migration. In the studies, downregulation of miR-425-5p expression suppressed pulmonary metastasis in the nude mice. Thus, miR-425-5p was demonstrated to have the potential to become a novel metastasis-associated gene; however, the mechanisms associated with these effects require further study. In the future, the development of miR-425-5p as a novel therapeutic strategy for the treatment of GC may be possible.