RUNX1-induced upregulation of PTGS2 enhances cell growth, migration and invasion in colorectal cancer cells.

Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499-981 bp) and (1053-1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086-1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.

Peptide encoded by lncRNA BVES-AS1 promotes cell viability, migration, and invasion in colorectal cancer cells via the SRC/mTOR signaling pathway.

Long non-coding RNAs (lncRNAs) have been revealed to harbor open reading frames (ORFs) that can be translated into small peptides. The peptides may participate in the pathogenesis of colorectal cancer (CRC). Herein, we investigated the role of a lncRNA BVES-AS1-encoded peptide in colorectal tumorigenesis. Through bioinformatic analysis, lncRNA BVES-AS1 was predicted to have encoding potential and to be associated with poor prognosis of patients with CRC. In CRC cells, BVES-AS1 was validated to encode a 50-aa-length micro-peptide, named BVES-AS1-201-50aa, through a western blotting method. BVES-AS1-201-50aa enhanced cell viability and promoted the migratory and invasive capacities of HCT116 and SW480 CRC cells in vitro, validated via CCK-8 assay and transwell assay, respectively. Immunofluorescence assay showed that BVES-AS1-201-50aa increased the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) in CRC cells. We further verified that BVES-AS1-201-50aa targeted and activated the Src/mTOR signaling pathway in CRC cells by co-immunoprecipitation (Co-IP) experiment, qualitative proteomic analysis, and western blotting. Our findings demonstrated that BVES-AS1 could encode a micro-peptide, which promoted CRC cell viability, migration, and invasion in vitro. Our current work broadens the diversity and breadth of lncRNAs in human carcinogenesis.

Endovascular thrombectomy versus standard medical treatment for stroke patients with acute basilar artery occlusion: a systematic review and meta-analysis.

BACKGROUND: Whether endovascular thrombectomy (EVT) is superior to standard medical treatment (SMT) for stroke patients with acute basilar artery occlusion (BAO) is uncertain. This systematic review and meta-analysis aimed to compare the safety and efficacy of EVT with SMT for treating BAO patients. METHODS: Papers were retrieved from PubMed, Embase, and the Cochrane Library databases. The primary outcome of this meta-analysis was favorable functional outcomes at 3 months (defined as a modified Rankin Scale (mRS) score of ≤3). A random effect model was used to calculate risk ratios (RR) with 95% confidence intervals (CIs) per outcome. RESULTS: Five articles, including two randomized controlled trials (RCTs) and four observational cohort studies, comprising 1484 patients (1024 in the EVT group and 460 in the SMT group), were included in the meta-analysis. The pooled results demonstrated no significant differences between the EVT and SMT groups in achieving favorable functional outcomes at 3 months (RR=1.63, 95% CI 0.90, 2.96; p=0.11). However, patients in the EVT group had higher rates for symptomatic intracerebral hemorrhage (RR=6.22, 95% CI 2.06 to 18.76; p=0.001) but lower mortality at 3 months (RR=0.72, 95% CI 0.56 to 0.91; p=0.007) than patients in the SMT group. CONCLUSION: Among patients with BAO, EVT and SMT did not differ significantly in achieving favorable functional outcomes at 3 months, but BAO patients treated with EVT might have lower mortality at 3 months. RCTs are warranted to further assess the efficacy and safety of EVT for BAO patients.

Endovascular Thrombectomy VS. Medical Treatment for Mild Stroke Patients: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: At present, endovascular thrombectomy (EVT) has been gradually became a standard therapy for stroke patients caused by emergent large-vessel occlusion (ELVO). However, the question about whether EVT is superior to medical treatment for mild stroke patients presenting with a low baseline National Institutes of Health Stroke Scale (NIHSS) score remains unclear. The aim of this systematic review and meta-analysis was to compare the safety and efficacy of EVT with medical treatment in mild stroke patients. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted through searching the PubMed, Embase and Cochrane Library databases. All statistical analyses were performed by using Review Manager 5.3 software. Primary outcomes of this meta-analysis were as follows: favorable functional outcome at 90 days (defined as a modified Rankin scale (mRS) score of 0-2); excellent functional outcome at 90 days (defined as a mRS score of 0-1); symptomatic intracerebral hemorrhage (sICH); mortality at 90 days. RESULTS: A total of 13 eligible studies with 2135 patients were included in this meta-analysis. The pooled results indicated that mild stroke patients underwent EVT had higher risk of sICH than those receiving medical treatment alone (OR = 3.21; 95% CI, 1.98-5.22; P < 0.001). In addition, no significant difference was found between the two groups in mortality at 90 days (OR = 1.80; 95% CI, 0.88-3.65; P=0.11). Meanwhile, no significant difference was found between the two groups in patients achieving favorable functional outcome at 90 days and excellent functional outcome at 90 days (OR = 1.10; 95% CI, 0.74-1.64; P = 0.65) (OR = 1.03; 95% CI, 0.79-1.35; P = 0.80). CONCLUSIONS: Our pooled results showed similar clinical outcomes at 90 days of EVT and medical treatment in mild stroke patients with ELVO, although patients underwent EVT had higher rates of sICH. However, due to several limitations of this meta-analysis, randomized controlled trials are needed to further evaluate the potential efficacy of EVT in mild stroke patients.

lncRNA TTN­AS1 upregulates RUNX1 to enhance glioma progression via sponging miR­27b­3p.

Long non­coding RNAs (lncRNAs) contribute to the tumorigeneses of numerous types of cancer, including glioma. The present study was designed to unveil a novel lncRNA functioning in glioma and explore the underlying mechanisms. lncRNA titin­antisense RNA1 (TTN­AS1), miR­27b­3p and Runt­related transcription factor 1 (RUNX1) expression in glioma tissues and cell lines was estimated by RT­qPCR. Si­TTN­AS1 was transfected into glioma cell lines (U251 and LN229), and CCK­8 assay, flow cytometry, wound healing and Transwell assays were applied to estimate the function of TTN­AS1 in glioma cells. miR­27b­3p inhibitor was used to explore the mechanisms. The results revealed that TTN­AS1 was highly expressed in glioma specimens and cell lines. Downregulation of TTN­AS1 inhibited the proliferation, migration and invasion of the glioma cells, as well as increased the rate of apoptosis. In vivo, the tumor growth was also inhibited by TTN­AS1 depletion in nude mice. Furthermore, we revealed that TTN­AS1 exerted oncogenic effects via sponging miR­27b­3p and thereby positively regulating RUNX1 expression. In conclusion, the present study supported that TTN­AS1 acts as an oncogene in glioma by targeting miR­27b­3p to release RUNX1. This finding may contribute to gene therapy of glioma.

Application of esophageal irradiation stents coated with 125I particles in advanced esophageal cancer.

PURPOSE: The current study was designed to investigate the primary efficacy of esophageal irradiation stents coated with 125I particles in the treatment of elderly patients with advanced esophageal cancer. METHODS: Forty-three elderly patients with advanced esophageal cancer were treated with esophageal stents in the First Affiliated Hospital of Xinxiang Medical University between September 2009 and December 2010. Patients were randomly divided into group A (N=18), treated with irradiation stents, and group B (N=25), treated with ordinary stents. There were no significant intergroup differences in age, lesion length, degree of stenosis, or cancer stage. The stent implantation success rate, relief of dysphagia and complication rate, and survival were assessed. RESULTS: The stent implantation success and short-term dysphagia relief rates were 100.0% in both groups. The mean survival time was 9.8 months and 4.8 months in groups A and B, respectively (p<0.01). However, no significant difference in pain (5/18) or esophageal restenosis (7/25) was found (both p>0.05). CONCLUSION: Dysphagia was relieved and survival was prolonged in advanced esophageal cancer cases treated with 125I particle-coated esophageal stents. This method may be superior to the traditional stents method.

Intermediate analysis of magnesium alloy covered stent for a lateral aneurysm model in the rabbit common carotid artery.

OBJECTIVE: To analyze the outcomes of a magnesium alloy covered stent (MACS) for a lateral aneurysm model in common carotid artery (CCA). METHODS: In 32 rabbits, a MACS (group A, n = 17) or a Willis covered stent (WCS; group B, n = 15) was inserted and the rabbits were sacrificed 1, 3, 6, or 12 months after stenting. Angiography and intravascular ultrasound (IVUS) were performed at 3, 6, and 12 months. Scanning electron microscopy was performed for six stents in each group at 1, 3, and 6 months, and histopathology and histomorphology were conducted at 3 (n = 4), 6 (n = 4), and 12 (n = 12) months. RESULTS: Final angiography showed complete occlusion of the aneurysms in 12 cases. IVUS at 6 and 12 months revealed a significant increase in mean lumen area of the stented CCA in group A and also showed greater mean lumen area in group A than in group B. The endothelialization process was quicker in group A than in group B. CONCLUSION: MACS is effective for occlusion of lateral aneurysms and is superior to WCS in growth of the stented CCA and endothelialization. Further work is needed to make this device available for human use. KEY POINTS: • The MACS is an effective approach for occlusion of a lateral aneurysm. • IVUS showed that the CCA could grow following degradation of the MACS. • The lumen area of the stented CCA was excellent in MACS. • HE staining displayed the degradation of the magnesium alloy stent. • Combination of IVUS and DSA were applied in this study.

Down-regulation of Rab17 promotes tumourigenic properties of hepatocellular carcinoma cells via Erk pathway.

The small GTPase, Ras-related protein 17 (Rab17), a member of the Rab family, plays a critical role in the regulation of membrane traffic in polarized eukaryotic cells. However, the role of Rab17 in hepatocellular carcinoma (HCC) is not clear. Clinical speciments reveal that Rab17 was present in 15 of 20 (75.0%) paraneoplastic tissues and 7 of 20 (35.0%) HCC samples (P=0.0248). To elucidate the tumourigenic role of Rab17 in HCC, we generated two Rab17 low-expressing HCC cell lines (Hep3B and Huh-7). The results showed that Rab17 down-regulation significantly promoted the tumourigenic properties of HCC cells in vitro and in vivo, as demonstrated by enhanced cell proliferation, colony formation, invasion and migration, decreased G1 arrest, and increased tumour xenograft growth and angiogenesis. However, the enhanced tumourigenic properties of HCC cells by Rab17 down-regulation was significantly inhibited by PD980592, the inhibitor of the Erk pathway, indicating that the Erk pathway plays a critical role in Rab17 down-regulation-induced enhanced tumourigenic properties of HCC cells. Our data provide a new insight into the essential role of Rab17 in HCC carcinogenesis and suggest that Rab17 expression might be tumor suppressor gene and might provide a new interventional therapeutic target for this common malignancy.

Silencing of hypoxia­inducible adrenomedullin using RNA interference attenuates hepatocellular carcinoma cell growth in vivo.

Adrenomedullin (ADM) is an angiogenic peptide that has been shown to increase the risk of endometrial hyperplasia and to promote tumor cell survival following hypoxia. ADM may induce microvessel proliferation and partially decrease hypoxia in solid tumors, thus contributing to the proliferation of tumor cells, as well as tumor invasion and metastasis. However, the impact of hypoxia­induced ADM expression on hepatocellular carcinoma (HCC) cells requires further elucidation. In the present study it was found that the levels of ADM mRNA in tumor tissue from patients with HCC were significantly increased compared with the mRNA levels in adjacent non­tumorous liver tissue. Under hypoxic conditions, the mRNA and protein levels of ADM, as well as those of the cancer­promoting genes vascular endothelial growth factor and hypoxia­inducible factor 1α, were significantly elevated in a time­dependent manner in three human HCC cell lines. In addition, knockdown of ADM expression using short hairpin RNA (shRNA) in SMMC­7721 cells resulted in apoptosis that was not observed in untransfected cells. Furthermore, combined treatment with cisplatin and ADM­shRNA significantly decreased tumor growth in vivo compared with treatment with cisplatin or ADM­shRNA alone. These data demonstrate that ADM acts as a critical promoter of cell cycle progression in HCC and that the inhibition of ADM may be an effective interventional therapeutic strategy in HCC.

RNA interference targeting adrenomedullin induces apoptosis and reduces the growth of human bladder urothelial cell carcinoma.

Adrenomedullin (ADM) is a potent, long-lasting angiogenic peptide that was originally isolated from human pheochromocytoma. ADM signaling is of particular significance in endothelial cell biology because the peptide protects cells from apoptosis, and ADM has been shown to be pro-tumorigenic in that it stimulates tumor cell growth and angiogenesis. ADM may be involved in micro-vessel proliferation and partially in the release of hypoxia in solid tumors, contributing to the proliferation of tumor cells as well as local tumor invasion and metastasis. However, the effect of hypoxia-induced ADM expression in bladder cancer remains unclear. Here, we found that the levels of ADM protein in tumor tissue from patients with bladder urothelial cell carcinoma were significantly increased compared to the adjacent non-tumor bladder tissues (p < 0.01). Under hypoxic conditions, the expression of ADM was significantly elevated in a time-dependent manner in human bladder cancer cell lines. Furthermore, the knockdown of ADM by shRNA in T24 cells showed obvious apoptosis compared to untransfected controls (p < 0.0001). In addition, the combination of cisplatin and ADM-shRNA significantly reduces the tumor growth in vivo compared to treatment with cisplatin (p = 0.0046) or ADM-shRNA alone (p < 0.0001). These data suggest that ADM plays an important role in promoting bladder cancer cell growth under hypoxia and that the inhibition of ADM may provide a target for bladder cancer therapy.