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.

Long noncoding RNAs (lncRNAs) have been proven to play critical roles in cancer progression. Recently, lncRNA MAGI2‐AS3 has been revealed to be a tumor suppressor and inhibit cell growth by targeting the Fas/FasL signalling pathway in breast cancer. However, the role and underlying mechanism of MAGI2‐AS3 in hepatocellular carcinoma (HCC) remain largely unknown. In the current study, we found that MAGI2‐AS3 expression is downregulated in HCC tissues and closely associated with some clinical characteristics (tumor size, lymph node metastasis, and TNM stage) and poor overall survival. Overexpression of MAGI2‐AS3 inhibits HCC cell proliferation and migration in vitro, while impedes tumor growth in vivo accordantly. In addition, our data suggest that MAGI2‐AS3 could function as an endogenous sponge of miR‐374b‐5p by directly binding to it and suppressing its expression. Furthermore, miR‐374b‐5p upregulation could restore the inhibitory effect of MAGI2‐AS3 on HCC cells processes. Moreover, suppressor with morphogenetic effect on genitalia family member 1 (SMG1) is positively regulated by MAGI2‐AS3 via absorbing miR‐374b‐5p in HCC cells. More important, SMG1 knockdown reverses the suppressive function of MAGI2‐AS3 in HCC cell processes. Taken together, we reveal a functional MAGI2‐AS3/miR‐374b‐5p/SMG1 axis that suppresses HCC progression, potently suggesting a new road for HCC treatment.

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We suggest that this lymphoma should be regarded as a unique DLBCL associated with chronic inflammation (DLBCL-CI) because of an indolent clinical behaviour to avoid excessive or unnecessary treatments. In addition, early accurate diagnosis and complete resection of this tumour are crucial for optimal patient outcome.