BackgroundCancer-associated fibroblasts (CAFs), one of the principal constituents of the tumor microenvironment, have a pivotal role in tumor progression. Dysregulation of microRNAs (miRNAs) in CAFs contributes to the tumor-promoting ability of CAFs. However, the mechanism underlying the involvement of miRNAs in CAFs of gastric cancer (GC) is not fully understood. This study aimed to explore the effects of miRNA-214 in CAFs on GC migration and invasion.MethodsThe primary CAFs and corresponding normal fibroblasts (NFs) were isolated. Cell counting kit-8, EdU cell proliferation staining and Transwell assays were used to determine the role of miRNA-214 in GC progression. Real-time polymerase chain reaction, Western blot analysis, and dual-luciferase reporter assay were performed to verify the target genes of miRNA-214. Immunofluorescence and Western blot analysis were applied to detect the expression of epithelial–mesenchymal transition (EMT) markers. Immunohistochemistry and in situ hybridization were implemented to analyze the fibroblast growth factor 9 (FGF9) and miRNA-214 expression in human GC tissues, respectively. Finally, to assess its prognostic relevance, Kaplan–Meier survival analysis was conducted.ResultsMiRNA-214 was significantly downregulated in CAFs of GC compared with NFs. The upregulation of miRNA-214 in CAFs inhibited GC cell migration and invasion in vitro but failed to affect proliferation. Moreover, GC cells cultured with conditioned medium from CAFs transfected with miR-214 mimic showed increased expression of E-cadherin and decreased expression of Vimentin, N-cadherin and Snail, indicating the suppression of EMT of GC cells. Furthermore, FGF9 was proved to be a direct target gene of miR-214. The expression of FGF9 was higher in CAFs than that in tumor cells not only in primary tumor but also in lymph node metastatic sites (30.0% vs 11.9%, P < 0.01 and 32.1% vs 12.3%, P < 0.01, respectively). Abnormal expression of FGF9 in CAFs of lymph node metastatic sites was significantly associated with poor prognosis in patients with GC (P < 0.05).ConclusionsThis study showed that miR-214 inhibited the tumor-promoting effect of CAFs on GC through targeting FGF9 in CAFs and regulating the EMT process in GC cells, suggesting miRNA-214/FGF9 in CAFs as a potential target for therapeutic approaches in GC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0995-9) contains supplementary material, which is available to authorized users.

Objectives Over the past years, growing attention has been paid to deciphering the pivotal role of long non‐coding RNAs (lncRNAs) in regulating the occurrence and development of human malignancies, cervical cancer (CC) included. Nonetheless, the regulatory role of lncRNA BBOX1 antisense RNA 1 (BBOX1‐AS1) has not been explored as yet. Material and Methods The expression of BBOX1‐AS1 was detected by reverse transcription real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell Counting Kit‐8 (CCK‐8), colony formation, TUNEL, Western blot, transwell and immunofluorescence assays testified the critical role of BBOX1‐AS1 in CC. The relationship between RNAs (BBOX1‐AS1, miR‐361‐3p, HOXC6 and HuR) was analysed by luciferase reporter, RNA Immunoprecipitation (RIP) and RNA pull‐down assays. Results BBOX1 antisense RNA 1 antisense RNA 1 was revealed to be highly expressed in CC. Decreased expression of BBOX1‐AS1 had suppressive effects on CC cell growth and migration. Molecular mechanism assays verified that BBOX1‐AS1 had negative interaction with miR‐361‐3p in CC. Additionally, homeobox C6 (HOXC6) was validated to be a downstream target of miR‐361‐3p in CC. Furthermore, ELAV‐like RNA‐binding protein 1, also known as HuR, was uncovered to be capable of regulating the mRNA stability of HOXC6 in CC. More importantly, rescue assays delineated that knockdown of HuR after overexpressing miR‐361‐3p could reverse BBOX1‐AS1 upregulation‐mediated effect on CC progression. Similarly, the function induced by BBOX1‐AS1 upregulation on CC progression could be countervailed by HOXC6 depletion. Conclusions BBOX1 antisense RNA 1 facilitates CC progression by upregulating HOXC6 expression via miR‐361‐3p and HuR.

Here, we report electronic and optoelectronic performance of multilayer InSe are effectively regulated by phase engineering. The electron mobility is increased to 22.8 cm V s for β-InSe FETs, which is 18 times higher than 1.26 cm V s of α-InSe FETs. The enhanced electronic performance is attributed to larger carrier sheet density and lower contact resistance. Multilayer β-InSe photodetector exhibits an ultrahigh responsivity of 8.8 × 10 A/W under 800 nm illumination, which is 574 times larger than 154.4 A/W of α-InSe photodetector. Our results demonstrate phase-engineering is a valid way to tune and further optimize electronic and optoelectronic performance of multilayer InSe nanodevices.

MicroRNAs (miRNAs) are differentially expressed and play crucial roles in cancer development and progression. Elevated glycolysis provides survival advantage and metastatic phenotype. Emerging evidence indicates that glycolysis in cancers can be regulated by miRNAs. In the present study, the role of miR-26b in the proliferation, invasion and glycolytic phenotype of osteosarcoma (OS) cells was investigated. miR-26b was reported to be downregulated in OS tissues, however, the effect of miR-26b on OS has not been distinctly evaluated. The present study therefore investigated the miR-26b sensitivity mechanism in OS. To determine the role of miR-26, we reinstated its expression in the U2OS OS cell line through transfection with miR-26b mimics and examined the effects on cell proliferation, migration, invasion, cell cycle progression and glycolytic parameters. The computational prediction tool was employed to identify the molecular target of miR-26b and was confirmed experimentally. Restoration of miR-26b expression inhibited cell proliferation, migration and invasion, arrested cell cycle progression, and induced cell apoptosis accompanied by the downregulation of glycolytic phenotype. Moreover, the binding site for miR-26b was predicted in the 3'UTR of gene 6-phosphofructo-2-kinase/fructose‑2,6-bisphosphatase-3 (PFKFB3), suggesting a role for miR-26b in metabolic alteration in OS cells. Further studies showed that overexpression of miR-26b repressed PFKFB3 mRNA and protein levels followed by modulation of the expression of glycolytic components (LDHA, GLUT-1) and markers of invasion and cell cycle such as MMP-9, MMP-2, cyclin D1 and p27. Collectively, the data suggested the tumor suppressive role of miR-26b which functions by targeting the glycolytic metabolism in OS cells, and providing a possible therapeutic strategy for OS patients by targeting miRNA expression.

BackgroundChemotherapy is one of major therapeutic regimens for neuroblastoma (NB) in children. However, recurrence and metastasis associated with poor prognosis caused by acquired multidrug resistance remains a challenge. There is a great need to achieve new insight into the molecular mechanism of drug resistance in NB. The aim of this study is to identify novel drug sensitivity-related biomarkers as well as new therapeutic targets to overcome chemoresistance.MethodsWe proteome-wide quantitatively compared protein expression of two NB cell lines with different drug sensitivities, isolated from the same patient prior to and following chemotherapy. Annexin A2 (ANXA2) emerged as a key factor contributing to drug resistance in NB. Then, we assessed the correlation of ANXA2 expression and clinical characteristics using a tissue microarray. Further, the roles of ANXA2 in chemoresistance for NB and the underlying mechanisms were studied by using short hairpin RNA (shRNA) in vitro and vivo.ResultsFirst in total, over 6000 proteins were identified, and there were about 460 significantly regulated proteins which were up- or down-regulated by greater than two folds. We screened out ANXA2 which was upregulated by more than 12-fold in the chemoresistant NB cell line, and it might be involved in the drug resistance of NB. Then, using a tissue chip containing 42 clinical NB samples, we found that strong expression of ANXA2 was closely associated with advanced stage, greater number of chemotherapy cycles, tumor metastasis and poor prognosis. Following knockdown of ANXA2 in NB cell line SK-N-BE(2) using shRNA, we demonstrate enhanced drug sensitivity for doxorubicin (2.77-fold) and etoposide (7.87-fold) compared with control. Pro-apoptotic genes such as AIF and cleaved-PARP were upregulated. Inhibiting ANXA2 expression attenuated transcriptional activity of NF-κB via down-regulated nuclear translocation of subunit p50. Finally, simulated chemotherapy in a xenograft NB nude mouse model suggests that ANXA2 knockdown could improve clinical results in vivo.ConclusionOur profiling data provided a rich source for further study of the molecular mechanisms of acquired drug resistance in NB. Further study may determine the role of ANXA2 as a prognostic biomarker and a potential therapeutic target for patients with multidrug-resistant NB.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0581-6) contains supplementary material, which is available to authorized users.

In this paper, we study the coexistence and synergy between edge and central cloud computing in heterogeneous cellular networks (HetNets), in which multi-antenna small base stations (SBSs) empowered by clouds at the edge offer computing services for user equipments (UEs), whereas a macro base station (MBS) provides computing services from a central cloud via a high-speed backhaul.With processing latency constraints at the edge cloud and backhaul, we aim to minimize the network energy consumption (the energy used for task offloading as well as computation) through jointly optimizing the cloud selection, the UE's transmit power, the SBS's receive beamformer, and the SBS's transmit covariance matrix. We devise a tractable solution that can achieve great performance gain over conventional schemes. With large-scale antennas at the MBS, the massive multiple-input multipleoutput (MIMO) backhaul can significantly reduce the complexity of our algorithm and obtain even better performance.

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Early studies indicate that graphite is feasible as the negative electrode of a potassium-ion battery, but its electrochemical performance still cannot meet the demands of applications. More efforts should be focused on increasing the specific capacity and improving the rate capability in the meantime. Thus, stainless-steel autoclave technology has been utilized to prepare phosphorus nanoparticles encapsulated in reduced graphene oxide matrix as the electrode materials for a potassium-ion battery. As a result, the composite matrix affords high reversible capacities of 354 and 253 mA h g at 100 and 500 mA g , respectively. The superior electrochemical performance is mainly because the composite matrix possesses better electronic conductivity and a robust structure, which can promote the electron-transfer performance of the electrode. Furthermore, phosphorus particles can contribute to the high capacity through an alloying mechanism. In addition, the silklike, ultrathin, film composite with a high surface area is conducive to capacitive potassium-ion storage, which plays a more important role in rate performance and a high current density capability.