Strategies targeted vascular endothelial growth factor (VEGF)-dependent osteosarcoma progression are limited although important progress has been made in illustrating the mechanisms. Here we identified circ_001621 as one of the significantly upregulated circular RNAs (circRNAs) by circRNAs microarrays. We found that patients with high circ_001621 expression had a shorter survival time. Moreover, we found several potential sponge micro RNAs (miRNA) of circ_001621 with Circular RNA Interactome database. Among the candidate sponge, we elucidated the association of circ_001621 and miR-578. In addition, we demonstrated that miR-578 targeted circ_001621 directly. Functionally, we set up the experimental system to investigate the effects of circ_001621/miR-578/VEGF interaction in vitro and in vivo. Results indicated circ_001621-promoted osteosarcoma proliferation and migration via attenuating the inhibition of cyclin-dependent kinase 4 (CDK4) and matrix metallopeptidase 9 (MMP9) by miR-578, respectively. Nude mice experiment was further performed to estimate the promotion of metastasis by circ_001621. The present study evaluated the mechanisms underlying circ_001621 enhanced osteosarcoma progression and provided novel therapeutic targets for advanced osteosarcoma.

Congenital heart defects (CHDs) are the most common group of major birth defects. Presently there are no clinically used biomarkers for prenatally detecting CHDs. Here, we performed a comprehensive maternal serum proteomics assessment, combined with immunoassays, for the discovery of non-invasive biomarkers for prenatal diagnosis of CHDs. A total of 370 women were included in this study. An isobaric tagging for relative and absolute quantification (iTRAQ) proteomic approach was used first to compare protein profiles in pooled serum collected from women who had CHD-possessing or normal fetuses, and 47 proteins displayed significant differential expressions. Targeted verifications were performed on 11 proteins using multiple reaction monitoring mass spectrometry (MRM-MS), and the resultant candidate biomarkers were then further validated using ELISA analysis. Finally, we identified a biomarker panel composed of 4 cytoskeletal proteins capable of differentiating CHD-pregnancies from normal ones [with an area under the receiver operating characteristic curve (AUC) of 0.938, P < 0.0001]. The discovery of cytoskeletal protein changes in maternal serum not only could help us in prenatal diagnosis of CHDs, but also may shed new light on CHD embryogenesis studies.

Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the anti-apoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADP-ribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.

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