Background Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are aberrantly expressed in various cancers. However, the functional roles of lncRNAs in breast cancer remain largely unknown. Methods Based on public databases and integrating bioinformatics analyses, the overexpression of lncRNA BCRT1 in breast cancer tissues was detected and further validated in a cohort of breast cancer tissues. The effects of lncRNA BCRT1 on proliferation, migration, invasion and macrophage polarization were determined by in vitro and in vivo experiments. Luciferase reporter assay and RNA immunoprecipitation (RIP) were carried out to reveal the interaction between lncRNA BCRT1, miR-1303, and PTBP3. Chromatin immunoprecipitation (ChIP) and RT-PCR were used to evaluate the regulatory effect of hypoxia-inducible factor-1α (HIF-1α) on lncRNA BCRT1. Results LncRNA BCRT1 was significantly upregulated in breast cancer tissues, which was correlated with poor prognosis in breast cancer patients. LncRNA BCRT1 knockdown remarkably suppressed tumor growth and metastasis in vitro and in vivo. Mechanistically, lncRNA BCRT1 could competitively bind with miR-1303 to prevent the degradation of its target gene PTBP3, which acts as a tumor-promoter in breast cancer. LncRNA BCRT1 overexpression could promote M2 polarization of macrophages, mediated by exosomes, which further accelerated breast cancer progression. Furthermore, lncRNA BCRT1 was upregulated in response to hypoxia, which was attributed to the binding of HIF-1α to HREs in the lncRNA BCRT1 promoter. Conclusions Collectively, these results reveal a novel HIF-1α/lncRNA BCRT1/miR-1303/PTBP3 pathway for breast cancer progression and suggest that lncRNA BCRT1 might be a potential biomarker and therapeutic target for breast cancer.

Background Exosomes from cancer cells or immune cells, carrying bio-macromolecules or microRNAs (miRNAs), participate in tumor pathogenesis and progression by modulating microenvironment. Our study aims to investigate the role of these microRNA-501-3p (miR-501-3p) containing exosomes derived from tumor-associated macrophage (TAM) in the progression of pancreatic ductal adenocarcinoma (PDAC). Methods Firstly, the function of TAM recruitment in PDAC tissues was assessed, followed by identification of the effects of M2 macrophage-derived exosomes on PDAC cell activities and tumor formation and metastasis in mice. In silico analysis was conducted to predict differentially expressed genes and regulatory miRNAs related to PDAC treated with macrophages, which determined miR-501-3p and TGFBR3 for subsequent experiments. Next, gain- and loss-of-function experiments were performed to examine their role in PDAC progression with the involvement of the TGF-β signaling pathway. Results TAM recruitment in PDAC tissues was associated with metastasis. Highly expressed miR-501-3p was observed in PDAC tissues and TAM-derived exosomes. Both M2 macrophage-derived exosomes and miR-501-3p promoted PDAC cell migration and invasion, as well as tumor formation and metastasis in nude mice. MiR-501-3p was verified to target TGFBR3. PDAC cells presented with down-regulated TGFBR3, which was further decreased in response to M2 macrophage treatment. TGF-β signaling pathway activation was implicated in the promotion of miR-501-3p in PDAC development. The suppression of macrophage-derived exosomal miR-501-3p resulted in the inhibition of tumor formation and metastasis in vivo. Conclusion M2 macrophage-derived exosomal miR-501-3p inhibits tumor suppressor TGFBR3 gene and facilitates the development of PDAC by activating the TGF-β signaling pathway, which provides novel targets for the molecular treatment of PDAC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1313-x) contains supplementary material, which is available to authorized users.

Human cancers, including hepatocellular carcinoma (HCC), are characterized by a high degree of drug resistance in chemotherapy. However, the underlying molecular mechanism remains unknown. To the role of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in the regulation of macrophage polarization, M1-type and M2-type macrophages were separately induced using lipopolysaccharide and interleukin-4 (IL-4), and we found that the IL-6/STAT3 signaling pathway was inhibited in M1-type macrophages but activated in M2-type macrophages. After anti-IL-6-treated macrophages were separately induced by lipopolysaccharide and IL-4, we found that the inhibition of IL-6/STAT3 signaling pathway turned macrophages into M1-type. Co-culture with M1-type macrophages reduced HCC cell viability, proliferation, invasion, migration, drug resistance, but increased apoptosis. Co-culture with M2-type macrophages yielded reciprocal results. The inhibition of IL-6/STAT3 signaling pathway mediated by anti-IL6 was shown to significantly enhance the effects of M1-type macrophages on HCC cells and rescue HCC cells from co-culture with M2-type macrophages. Tumor xenografts of co-cultured HCC cells were established in nude mice and the results showed that the inhibition of IL-6/STAT3 signaling pathway mediated by anti-IL6 was found to reduce tumor formation of HCC cells co-cultured with M1- or M2-type macrophages and lung metastases. The current study reveals a novel mechanism of IL-6/STAT3 signaling pathway in the regulation of macrophage polarization, thus contributing to HCC metastasis and drug resistance in chemotherapy.

BackgroundThe aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence.MethodsA multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.ResultsA total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).ConclusionPollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.