CircFLNA Acts as a Sponge of miR-646 to Facilitate the Proliferation, Metastasis, Glycolysis, and Apoptosis Inhibition of Gastric Cancer by Targeting PFKFB2.

BACKGROUND: Many studies have confirmed that circular (circRNA) is involved in the development of gastric cancer (GC). However, the role of circFLNA in the progression of GC remains unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was used to measure the relative expression of circFLNA, microRNA (miR)-646 and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 2 (PFKFB2). Cell counting kit 8 (CCK8) assay, transwell assay and flow cytometry were performed to determine the proliferation, migration, invasion and apoptosis of cells, respectively. GC tumor xenograft models were built to confirm the function of circFLNA silencing on GC tumor growth in vivo. Furthermore, the lactate production, glucose consumption, ATP level and glucose uptake were detected to assess the glycolysis of cells. Then, the interaction between miR-646 and circFLNA or PFKFB2 was confirmed using dual-luciferase reporter assay. RNA immunoprecipitation (RIP) assay was used to verify the interaction between miR-646 and circFLNA further. In addition, Western blot (WB) analysis was employed to detect the relative protein expression of PFKFB2. RESULTS: Our results found that circFLNA was upregulated in GC tissues and cells. Silencing of circFLNA could suppress the proliferation, migration, invasion, glycolysis, and enhance the apoptosis of GC cells. Also, circFLNA knockdown reduced GC tumor volume and weight in vivo. Further experiments revealed that circFLNA could sponge miR-646, and miR-646 could target PFKFB2. The rescue experiments indicated that miR-646 inhibitor could reverse the suppressive effect of circFLNA silencing on GC progression, and PFKFB2 overexpression also could invert the inhibition effect of miR-646 on GC progression. CONCLUSION: Our data concluded that circFLNA played a pro-cancer role in GC, which suggested that circFLNA might be a potential biomarker for GC treatment.

MicroRNA-21 as a diagnostic marker for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: MicroRNA-21 (miR-21) is one of the oncogenic miRNAs which may be a potential diagnostic biomarker for hepatocellular carcinoma (HCC). METHODS: We systematically searched Medline, Embase, the Cochrane Library, ISI Web of Knowledge, Scopus from inception to August 15, 2018, and reference lists of identified primary studies. Two independent investigators extracted patient and study characteristics. The sensitivity and specificity of microRNA-21 for HCC detection and were analyzed with a random effect model. The area under summary receiver operating characteristic curve (AUC) was used to estimate overall test performance. RESULTS: A total of 515 HCC patients, and 338 healthy or chronic hepatitis controls from six published studies were enrolled in this meta-analysis. All articles were published in English with moderate-to-high quality. The overall pooled sensitivity and specificity were 85.2% (73.3% to 88.4%) and 79.2% (68.4% to 87.0%), respectively. The AUC area was 0.89 (95% CI: 0.85-0.91). The studies had moderate heterogeneity (I2=70.11%). None of the subgroups investigated-ethnicity, controls, sample source-could account for the heterogeneity. CONCLUSION: MiR-21 is a helpful biomarker for early diagnosis of HCC. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, erological tests and imaging examinations for HCC surveillance.

Low expression levels of plasma miR-141 are associated with susceptibility to gastric cancer.

MicroRNAs (miRNAs/miRs) offer great potential as biomarkers for the early detection and prognosis of cancer, and the discovery of miRNAs associated with gastric cancer is required. In the present study, the differences in the plasma expression levels of miR-141 between patients with gastric cancer and healthy controls, and the role of miR-141 in gastric cancer cell oncogenesis were investigated. A follow-up study of 164 patients with gastric cancer who underwent tumor resection was conducted, and comparisons with healthy control subjects were drawn. To investigate the biological functions of miR-141, a series of in vitro and in vivo assays were conducted, including proliferation, wound-healing and Transwell assays, and a xenograft tumor model. The results demonstrated that miR-141 expression was significantly decreased in tumor tissues compared with in healthy tissues (P<0.05). Kaplan-Meier analysis revealed improved survival benefits with increased miR-141 expression (as determined using the log-rank test, P<0.001), and multivariate Cox regression analysis revealed that patients with decreased expression levels of miR-141 carried a greater risk of death (hazard ratio=2.352; 95% CI=1.379-4.012; P=0.002). The downregulation of miR-141 was also associated with WHO staging, particularly for lymph node and distant metastasis. Exogenous overexpression of miR-141 significantly inhibited the proliferative and migratory abilities of the gastric cancer cell line BGC-823. In vivo studies also demonstrated that exogenous overexpression of miR-141 in BGC-823 cells markedly reduced tumor growth in nude mice. The present study revealed that increased miR-141 expression may be a positive prognostic factor, which may be clinically beneficial in patients with gastric cancer.

Efficacy of Therapeutic Endoscopy for Gastrointestinal Lesion (GI): A network meta-analysis.

OBJECTIVE: Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this systematic review was to compare the different modalities of endoscopic therapy for GI bleeding. METHODS: Studies were identified by searching electronic databases MEDLINE. We selected all available clinical studies published after 2000 that assessed efficacy and/or safety of different endoscopic hemostatic techniques in treating GI bleeding. The outcomes evaluated included initial hemostasis, rebleeding rate, and 30-day all-cause mortality. Network meta-analyses were performed to summarize the treatment effects. RESULTS: Total 20 studies involving 1845 patients were evaluated. Ten different treatment categories including mechanic, ablative, injection, and combined therapy were compared in our analysis in terms of their efficacy in stopping bleeding and complications. Band ligation [rate: 0.757; 95% Credible Interval (0.565, 0.887)] and injection therapy [rate: 0.891; 95% CI (0.791, 0.944)] had inferior efficacy in attaining initial hemostasis compared to others. Combined therapy of band ligation and HPC and hemoclip may represent the best options for preventing rebleeding and mortality respectively. No significant difference was found among other treatments in terms of complications. CONCLUSIONS: We recommend the application of hemoclips in treating GI bleeding due to its high hemostasis efficacy and low risk of 30-day mortality.

Increased expression of high-mobility group A2: A novel independent indicator of poor prognosis in patients with esophageal squamous cell carcinoma.

PURPOSE: Although high-mobility group A2 (HMGA2) protein has been reported to participate in cancer progression and metastasis, its clinical relationship with tumor invasion, lymph node metastasis, and prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to analyze the clinical and prognostic significance of HMGA2 in ESCC patients after curative resection. MATERIALS AND METHODS: The expression of HMGA2 protein was evaluated by using immunohistochemistry in a tissue microarray (TMA) containing ESCC lesions and adjacent normal esophageal epithelial tissues from 96 patients who had undergone curative resection. TMA was constructed by Shanghai Biochip Co. Ltd., Shanghai, China. The relationship between HMGA2 expression and clinicopathological parameters and prognosis was further analyzed. RESULTS: HMGA2 expression was significantly higher in ESCC tissues compared with that of the adjacent noncancerous tissues (P < 0.001). High expression of HMGA2 was significantly related to tumor size, lymph node metastasis, and advanced tumor-node-metastasis stage (P < 0.05). Patients with low expression of HMGA2 had a better prognosis than those with high expression (χ2 = 5.069, P = 0.024). Univariate analysis showed that age (P = 0.041), depth of tumor invasion (P = 0.031), lymph node status (P = 0.001), and HMGA2 expression (P = 0.024) were correlated with prognosis. Multivariate analysis showed that HMGA2 expression (hazard ratio [HR]: 0.539; 95% confidence interval [95% CI]: 0.302-0.963, P = 0.037) and lymph node metastasis (HR: 0.504; 95% CI: 0.310-0.820, P = 0.006) were independent prognostic factors for overall survival. CONCLUSIONS: High HMGA2 expression was related to lymph node metastasis and poor prognosis in ESCC. Our results indicated that HMGA2 could act as a potential biomarker for prognosis evaluation of ESCC patients.