Although CircRNA_100269 is a biomarker used to predict cancer recurrence, its expression and function in gastric cancer (GC) remain unknown. In this study, the expression of circRNA_100269 and its potential downstream miRNA targets were investigated. The molecular function and regulatory mechanism of circRNA_100269 in GC cell lines were also elucidated. The expression levels of circRNA_100269 and its linear isomer LPHN2 mRNA were found to be downregulated (p<0.01) in GC tissues. The target miRNA was predicted to be miR-630, whose expression was upregulated (p<0.01) and found to be negatively correlated with that of circRNA_100269 (r = −0.688) in GC tissues. Moreover, direct interaction of circRNA_100269 and miR-630 was confirmed through dual-luciferase assays. Overexpressing the circRNA_100269 plasmid inhibited cell proliferation (p<0.05). Furthermore, transfection of miR-630 mimics into cell lines overexpressing circRNA_100269 blocked the function of circRNA_100269 (p<0.05). Thus, circRNA_100269 level was downregulated in GC and correlated negatively with that of miR-630. Taken together, our results suggest that circRNA_100269 and miR-630 comprise a novel pathway that regulates proliferation of GC cells.

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BackgroundAcute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment.MethodsWe tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific single-chain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-ζ signaling domain. We further investigate the function of CLL-1 CAR-T cells.ResultsThe CLL-1 CAR-T cells specifically lysed CLL-1+ cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1+ myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression.ConclusionsCLL-1 CAR-T represents a promising immunotherapy for the treatment of AML.Electronic supplementary materialThe online version of this article (10.1186/s13045-017-0553-5) contains supplementary material, which is available to authorized users.

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