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.

Long non-coding 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 titin-antisense RNA1 (TTN-AS1), miR-27b-3p and Runt-related transcription factor 1 (RUNX1) expression in glioma tissues and cell lines was estimated by RT-qPCR. Si-TTN-AS1 was transfected into glioma cell lines (U251 and LN229), and CCK-8 assay, flow cytometry, wound healing and Transwell assays were applied to estimate the function of TTN-AS1 in glioma cells. miR-27b-3p inhibitor was used to explore the mechanisms. The results revealed that TTN-AS1 was highly expressed in glioma specimens and cell lines. Downregulation of TTN-AS1 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 TTN-AS1 depletion in nude mice. Furthermore, we revealed that TTN-AS1 exerted oncogenic effects via sponging miR-27b-3p and thereby positively regulating RUNX1 expression. In conclusion, the present study supported that TTN-AS1 acts as an oncogene in glioma by targeting miR-27b-3p to release RUNX1. This finding may contribute to gene therapy of glioma.

BackgroundWhether 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.MethodsPapers 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.ResultsFive 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.ConclusionAmong 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.

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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 hypoxia‑induced 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 non‑tumorous liver tissue. Under hypoxic conditions, the mRNA and protein levels of ADM, as well as those of the cancer‑promoting genes vascular endothelial growth factor and hypoxia‑inducible factor 1α, were significantly elevated in a time‑dependent manner in three human HCC cell lines. In addition, knockdown of ADM expression using short hairpin RNA (shRNA) in SMMC‑7721 cells resulted in apoptosis that was not observed in untransfected cells. Furthermore, combined treatment with cisplatin and ADM‑shRNA significantly decreased tumor growth in vivo compared with treatment with cisplatin or ADM‑shRNA 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.