CircMAN1A2 promotes vasculogenic mimicry of nasopharyngeal carcinoma cells through upregulating ERBB2 via sponging miR-940.

Nasopharyngeal carcinoma (NPC) is the most prevalent human primary malignancy of the head and neck, and the presence of vasculogenic mimicry (VM) renders anti-angiogenic therapy ineffective and poorly prognostic. However, the underlying mechanisms are unclear. In the present study, we used miR-940 silencing and overexpression for in vitro NPC cell EdU staining, wound healing assay and 3D cell culture assay, and in vivo xenograft mouse model and VM formation to assess miR-940 function. We found that ectopic miR-940 expression reduced NPC cell proliferation, migration and VM, as well as tumorigenesis in vivo. By bioinformatic analysis, circMAN1A2 was identified as a circRNA that binds to miR-940. Mechanistically, we confirmed that circMAN1A2 acts as a sponge for miR-940, impairs the inhibitory effect of miR-940 on target ERBB2, and then activates the PI3K/AKT/mTOR signaling pathway using RNA-FISH, dual luciferase reporter gene and rescue analysis assays. In addition, upregulation of ERBB2 expression is associated with clinical staging and poor prognosis of NPC. Taken together, the present findings suggest that circMAN1A2 promotes VM formation and progression of NPC through miR-940/ERBB2 axis and further activates the PI3K/AKT/mTOR pathway. Therefore, circMAN1A2 may become a biomarker and therapeutic target for anti-angiogenic therapy in patients with nasopharyngeal carcinoma.

Overexpression of macrophage-colony stimulating factor-1 receptor as a prognostic factor for survival in cancer: A systematic review and meta-analysis.

BACKGROUND: The relation between the expression of macrophage-colony stimulating factor-1 receptor (CSF-1R) and prognosis of cancer patients has been evaluated in multiple studies, but the results remain controversial. We, therefore, performed a meta-analysis and systematic review to figure out the role of CSF-1R in the prognosis of patients with cancer. METHODS: Several databases were searched, including Web of Science, PubMed, and EMBASE. All human studies were published as full text. The Newcastle-Ottawa risk of bias scale was applied to evaluate the research. We extracted hazard ratios (HRs) with 95% confidence interval (95% CI) which assessed progression-free survival (PFS) and overall survival (OS) in order to assess the impacts of CSF-1R on the prognosis of cancer patients. RESULTS: A total of 12 citations were identified, with studies including 2260 patients in different cancer types that met the eligibility criteria. It was suggested in a pooled analysis that the over-expression of CSF-1R was significantly related to worse PFS (HR: 1.68; P < .001, 1.25-2.10, 95% CI) and also poorer OS (HR=1.28; P < .001, 1.03-1.54, 95% CI). Analysis in subgroups indicated over-expressed CSF-1R was significantly associated with worse OS in hematological malignancy (HR = 2.29; P < .001, 1.49-3.09, 95% CI; model of fixed-effects; I2 = 0.0%, P < .001). Sensitivity analysis suggested that there was no study influencing the stability of the results. CONCLUSIONS: The overexpression of CSF-1R was significantly predictive of worse prognosis in those who suffer from different kinds of malignancies, particularly in hematological malignancy, which indicates that it might be a potential biomarker of prognosis in cancer survival and a potential molecular target in the treatment of malignant tumors.