BackgroundThe function of a new long non-coding RNA linc00673 remains unclear. While identified as an oncogenic player in non-small cell lung cancer (NSCLC), linc00673 was found to be anti-oncogenic in pancreatic ductal adenocarcinoma (PDAC). However whether linc00673 regulated malignancy and epithelial mesenchymal transition (EMT) has not been characterized.MethodsCell proliferation was assessed using CCK-8 and EdU assays, and cell migration and invasion were assessed using scratch assays and transwell invasion assays. Epithelial mesenchymal transition was examined using western blot, qRT-PCR and immunofluorescence staining. Interaction between miRNA and linc00673 was determined using luciferase reporter assays. In vivo experiments were performed to assess tumor formation. In addition, the expression data of NSCLC specimens of TCGA and patient survival data were utilized to explore the prognostic significance of linc00673.ResultsIn the present study, we found high linc00673 expression was associated with poor prognosis of NSCLC patients. In vitro experiments showed linc00673 knockdown reversed TGF-β induced EMT, and miR-150-5p was predicted to target linc00673 through bioinformatics tools. Overexpression of miR-150-5p suppressed lin00673’s expression while inhibition of miR-150-5p led to significant upregulation of lin00673, suggesting that linc00673 could be negatively regulated by miR-150-5p, which was further confirmed by the inverse correlation between linc00673 and miR-150-5p in NSCLC patients’ specimen. Furthermore, we proved that miR-150-5p could directly target linc00673 through luciferase assay, so linc00673 could sponge miR-150-5p and modulate the expression of a key EMT regulator ZEB1 indirectly. In addition, miR-150-5p inhibition abrogated linc00673 silence mediated proliferation, migration, invasion and EMT suppressing effect. Moreover, the inhibition of linc00673 significantly attenuated the tumorigenesis ability of A549 cells in vivo.ConclusionsWe validated linc00673 as a novel oncogenic lncRNA and demonstrated the molecular mechanism by which it promotes NSCLC, which will advance our understanding of its clinical significance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0685-9) contains supplementary material, which is available to authorized users.

BackgroundDairy products are major components of daily diet and the association between consumption of dairy products and public health issues has captured great attention. In this study, we conducted a meta-analysis to investigate the association between dairy products intake and cancer mortality risk.MethodsAfter a literature search in PubMed and EMBASE, 11 population-based cohort studies involving 778,929 individuals were considered eligible and included in the analyses. Data were extracted and the association between dairy products intake and cancer mortality risk was estimated by calculating pooled relative risks (RRs) and corresponding 95 % confidence intervals (CIs). Sensitivity analyses and subgroup analyses based on regions, genders and dairy types were performed as well. Potential dose–response relationship was further explored by adopting the generalized least squares (GLST) method.ResultsTotal dairy products intake was not associated with all cancer mortality risk, with the pooled RR of 0.99 (95 % CI 0.92–1.07, p = 0.893). Subgroup analyses showed that the pooled RRs were 0.97 (95 % CI 0.92–1.03, p = 0.314) for milk, 0.88 (95 % CI 0.71–1.10, p = 0.271) for yogurt, 1.23 (95 % CI 0.94–1.61, p = 0.127) for cheese and 1.13 (95 % CI 0.89–1.44, p = 0.317) for butter in male and female, however the pooled RR was 1.50 (95 % CI 1.03–2.17, p = 0.032) for whole milk in male, which was limited to prostate cancer. Further dose–response analyses were performed and we found that increase of whole milk (serving/day) induced elevated prostate cancer mortality risk significantly, with the RR of 1.43 (95 % CI 1.13–1.81, p = 0.003).ConclusionsTotal dairy products intake have no significant impact on increased all cancer mortality risk, while low total dairy intake even reduced relative risk based on the non-linear model. However, whole milk intake in men contributed to elevated prostate cancer mortality risk significantly. Furthermore, a linear dose–response relationship existed between increase of whole milk intake and increase of prostate cancer mortality risk.

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Ovarian cancer is one of the most common gynecological malignancies with a highly immunosuppressive tumor microenvironment (TME) and poor prognosis. Circular RNA (circRNA) is a type of non-coding RNA with high stability, which has been shown to play an important role in biological processes and TME reprogramming in a variety of tumors. The biological function of a novel circRNA, circATP2B4, in epithelial ovarian cancer (EOC) was detected and evaluated. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of extracellular vesicles (EVs)-packaged circATP2B4. Macrophage uptake of circATP2B4 was determined by EVs tracing. Dual luciferase reporter, fluorescence in situ hybridization (FISH), Western blotting (WB), and flow cytometry (FCM) assays were used to investigate the interactions between circATP2B4 and miR-532-3p as well as SREBF1 expression in macrophages. CircATP2B4 was upregulated in EOC tissues and positively correlated with ovarian cancer progression. Functionally, circATP2B4 promoted carcinogenic progression and metastasis of EOC both in vitro and in vivo. Mechanistically, extracellular vesicle-packaged circATP2B4 in EOC could be transmitted to infiltrated macrophages and acted as competing endogenous RNA (ceRNA) of miR-532-3p to relieve the repressive effect of miR-532-3p on its target SREBF1. Furthermore, circATP2B4 induced macrophage M2 polarization by regulating the miR-532-3p/SREBF1/PI3Kα/AKT axis, thereby leading to immunosuppression and ovarian cancer metastasis. Collectively, these data indicate that circATP2B4-containing EVs generated by EOC cells promoted M2 macrophages polarization and malignant behaviors of EOC cells. Thus, targeting EVs-packaged circATP2B4 may provide a potential diagnosis and treatment strategy for ovarian cancer.

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