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BackgroundTGF-β promotes tumor invasion and metastasis through inducing epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in human cancers. However, whether and how circRNAs contribute to TGF-β-induced EMT and metastasis in NSCLC remain vague. Here, we investigated the regulation and function of Circular RNA hsa_circ_0008305 (circPTK2) in TGF-β-induced EMT and tumor metastasis, as well as a link between circPTK2 and transcriptional intermediary factor 1 γ (TIF1γ) in NSCLC.MethodsCircular RNAs were determined by human circRNA Array analysis, real-time quantitative reverse transcriptase PCR and northern blot. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were employed to test the interaction between circPTK2 and miR-429/miR-200b-3p. Ectopic overexpression and siRNA-mediated knockdown of circPTK2, TGF-β-induced EMT, Transwell migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPTK2. Transcription and prognosis analyses were done in public databases.ResultsCircPTK2 and TIF1γ were significantly down-regulated in NSCLC cells undergoing EMT induced by TGF-β. CircPTK2 overexpression augmented TIF1γ expression, inhibited TGF-β-induced EMT and NSCLC cell invasion, whereas circPTK2 knockdown had the opposite effects. CircPTK2 functions as a sponge of miR-429/miR-200b-3p, and miR-429/miR-200b-3p promote TGF-β-induced EMT and NSCLC cell invasion by targeting TIF1γ. CircPTK2 overexpression inhibited the invasion-promoting phenotype of endogenous miR-429/miR-200b-3p in NSCLC cells in response to TGF-β. CircPTK2 overexpression significantly decreased the expression of Snail, an important downstream transcriptional activator of TGF-β/Smad signaling. In an in vivo experiment of metastasis, circPTK2 overexpression suppressed NSCLC cell metastasis. Moreover, circPTK2 expression was dramatically down-regulated and positively correlated with TIF1γ expression in human NSCLC tissues. Especially, circPTK2 was significantly lower in metastatic NSCLC tissues than non-metastatic counterparts.ConclusionOur findings show that circPTK2 (hsa_circ_0008305) inhibits TGF-β-induced EMT and metastasis by controlling TIF1γ in NSCLC, revealing a novel mechanism by which circRNA regulates TGF-β-induced EMT and tumor metastasis, and suggesting that circPTK2 overexpression could provide a therapeutic strategy for advanced NSCLC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0889-7) contains supplementary material, which is available to authorized users.

Strategies to control neovascularization in damaged tissues remain a key issue in regenerative medicine. Unlike most reported desferrioxamine (DFO)-loaded systems where DFO demonstrates a burst release, here we attain zero-order release behavior above 40 days. This outcome was achieved by blending DFO with silk nanofibers with special hydrophilic–hydrophobic properties. The special silk nanofibers showed strong physical binding capacity with DFO, avoiding chemical cross-linking. Using these new biomaterials in vivo in a rat wound model suggested that the DFO-loaded silk nanofiber hydrogel systems stimulated angiogenesis by the sustained release of DFO, but also facilitated cell migration and tissue ingrowth. These features resulted in faster formation of a blood vessel network in the wounds, as well improved healing when compared to the free DFO system. The DFO-loaded systems are also suitable for the regeneration of other tissues, such as nerve and bone, suggesting universality in the biomedical field.

Long non-coding RNAs (lncRNAs) have been involved in the process of cancer occurrence, progression, and treatment. Lung cancer-related lncRNAs are still an emerging field, thus we sought to identify novel functional lncRNAs as candidate targets in lung cancer. Here, we identified one novel lncRNA, MUC5B-AS1 (Ensembl: ENST00000532061.2). MUC5B-AS1 was upregulated in lung adenocarcinoma tissues compared with normal lung tissues. Moreover, MUC5B-AS1 promoted lung cancer cell migration and invasion in vitro and promoted lung cancer cell metastasis in vivo. MUC5B-AS1 and its cognate sense transcript MUC5B were highly co-expressed and mutually regulated in lung adenocarcinoma. Mechanistically, MUC5B-AS1 promoted cell migration and invasion by forming an RNA–RNA duplex with MUC5B, thereby increasing MUC5B expression levels in lung adenocarcinoma. The high expression of MUC5B was significantly associated with poor outcomes in lung adenocarcinoma. Our findings highlight MUC5B-AS1 functions as an oncogenic lncRNA in tumor metastasis and implicate MUC5B-AS1 as an attractive candidate target for lung adenocarcinoma treatment.

Epidemiological evidence indicates that vitamin D is involved in defense against diabetes; however, the precise underlying mechanism remains to be elucidated. In the present study, the effect of vitamin D on the pathogenesis of diabetes was investigated, with an emphasis on its direct effect on pancreatic β‑cells. A streptozotocin (STZ)‑induced type 1 diabetes mellitus (T1DM) mouse model and MIN6 mouse insulinoma β‑cells were subjected to vitamin D treatment. Histopathological analysis of pancreatic islets was performed to investigate insulitis, and reverse transcription-quantitative polymerase chain reaction and western blotting were used to determine the mRNA and protein expression levels of markers of autophagy [microtubule-associated protein 1A/1B‑light chain 3 (LC3) and Beclin 1] and regulation of apoptosis [B-cell lymphoma 2 (Bcl-2)]. Apoptosis of MIN6 cells was examined by flow cytometry following annexin V/propidium iodide labeling. The secretion of insulin was measured by ELISA. The results revealed that vitamin D reduced the incidence of T1DM, enhanced insulin secretion and relieved pancreatic inflammation in STZ‑treated mice. Furthermore, vitamin D increased the mRNA expression levels of LC3 and Beclin 1, and increased Bcl‑2 protein expression levels in STZ‑treated MIN6 cells, while decreasing the apoptosis rate. The results of the present study demonstrated, for the first time to the best of our knowledge, that vitamin D induces autophagy and suppresses apoptosis of pancreatic β‑cells, as well as preventing insulitis. These findings regarding vitamin D provide insights into its involvement in diabetes, and suggest a potential novel strategy for the treatment of diabetes via agents enhancing autophagy in pancreatic β-cells.