BackgroundThe metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC) is not fully elucidated.MethodsThe expressions of miR-193a (miR-193a-5p) in human lung cancer tissues and cell lines were detected by real-time PCR. Dual-luciferase reporter assay was used to identify the direct target of miR-193a. Cell proliferation, apoptosis, and metastasis were assessed by CCK-8, flow cytometry, and Transwell assay, respectively.ResultsThe expression of miR-193a in lung cancer tissues was decreased comparing to adjacent non-tumor tissues due to DNA hypermethylation in lung cancer tissues. Ectopic expression of miR-193a inhibited cell proliferation, colony formation, migration, and invasion in A549 and H1299 cells. Moreover, overexpression of miR-193a partially reversed tumor growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in NSCLC cells. Mechanistically, miR-193a reduced the expression of WT1, which negatively regulated the protein level of E-cadherin, suggesting that miR-193a might prevent EMT via modulating WT1-E-cadherin axis. Importantly, knockdown of WT1 resembled the anti-cancer activity by miR-193a and overexpression of WT1 partially reversed miR-193a-induced anti-cancer activity, indicating that WT1 plays an important role in miR-193a-induced anti-cancer activity. Finally, overexpression of miR-193a decreased the growth of tumor xenografts in mice.ConclusionCollectively, our results have revealed an important role of miR-193a-WT1-E-cadherin axis in metastasis, demonstrated an important molecular cue for EMT, and suggested a therapeutic strategy of restoring miR-193a expression in NSCLC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0450-8) contains supplementary material, which is available to authorized users.

BackgroundAcute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignancies due to sophisticated genetic mutations and epigenetic dysregulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, are important regulators of gene expression in all biological processes, including leukemogenesis. Recently, miR-375 has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-leukemia activity in AML is largely unknown.MethodsQuantitative reverse transcriptase PCR (qRT-PCR) was used to measure the expression of miR-375 and HOXB3 in leukemic cells and normal controls. Targets of miR-375 were confirmed by western blot and luciferase assay. Phenotypic effects of miR-375 overexpression and HOXB3 knockdown were assessed using viability (trypan blue exclusion assay), colony formation/replating, as well as tumor xenograft assays in vivo.ResultsThe expression of miR-375 was substantially decreased in leukemic cell lines and primary AML blasts compared with normal controls, because DNA hypermethylation of precursor-miR-375 (pre-miR-375) promoter was discovered in leukemic cells but not in normal controls. Lower expression of miR-375 predicted poor outcome in AML patients. Furthermore, forced expression of miR-375 not only decreased proliferation and colony formation in leukemic cells but also reduced xenograft tumor size and prolonged the survival time in a leukemia xenograft mouse model. Mechanistically, overexpression of miR-375 reduced HOXB3 expression and repressed the activity of a luciferase reporter through binding 3′-untranslated regions (3’-UTR) of HOXB3 mRNA. Overexpression of HOXB3 partially blocked miR-375-induced arrest of proliferation and reduction of colony number, suggesting that HOXB3 plays an important role in miR-375-induced anti-leukemia activity. Knockdown of HOXB3 by short hairpin RNAs reduced the expression of cell division cycle associated 3 (CDCA3), which decreased cell proliferation. Furthermore, HOXB3 induced DNA methyltransferase 3B (DNMT3B) expression to bind in the pre-miR-375 promoter and enhanced DNA hypermethylation of pre-miR-375, leading to the lower expression of miR-375.ConclusionsCollectively, we have identified a miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry which contributes to leukemogenesis and suggests a therapeutic strategy of restoring miR-375 expression in AML.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4097-z) contains supplementary material, which is available to authorized users.

Testing climatic niche divergence and modeling habitat suitability under conditions of climate change are important for developing strategies to limit the introduction and expansion of alien invasive weeds ( AIW s) and providing important ecological and evolutionary insights. We assessed climatic niches in both native and invasive ranges as well as habitat suitability under climate change for eight representative Chinese AIW s from the American continent. We used climatic variables associated with occurrence records and developed ecological niche models with Maxent. Interestingly, the climatic niches of all eight AIW s diverged significantly between the native and invasive ranges (the American continent and China). Furthermore, the AIW s showed larger climatic niche breadths in the invasive ranges than in the native ranges. Our results suggest that climatic niche shifts between native and invasive ranges occurred. Thus, the occurrence records of both native and invasive regions must be considered when modeling and predicting the spatial distributions of AIW s under current and future climate scenarios. Owing to high habitat suitability, AIW s were more likely to expand into regions of low latitude, and future climate change was predicted to result in a shift in the AIW s in Qinghai and Tibet (regions of higher altitude) as well as Heilongjiang, Jilin, Liaoning, Inner Mongolia, and Gansu (regions of higher latitude). Our results suggest that we need measures to prevent and control AIW expansion at the country‐wide level.

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