Long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis, exemplified by the recent finding that lncRNA maternally expressed gene 3 (MEG3) inhibits tumor growth in a p53-dependent manner. Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults, and TP53 mutations or loss are frequently detected in patients with therapy-related AML or AML with complex karyotype. Here, we reveal that MEG3 is significantly downregulated in AML and suppresses leukemogenesis not only in a p53-dependent, but also a p53-independent manner. In addition, MEG3 is proven to be transcriptionally activated by Wilms’ tumor 1 (WT1), dysregulation of which by epigenetic silencing or mutations is causally involved in AML. Therefore MEG3 is identified as a novel target of the WT1 molecule. Ten–eleven translocation-2 (TET2) mutations frequently occur in AML and significantly promote leukemogenesis of this disorder. In our study, TET2, acting as a cofactor of WT1, increases MEG3 expression. Taken together, our work demonstrates that TET2 dysregulated WT1-MEG3 axis significantly promotes AML leukemogenesis, paving a new avenue for diagnosis and treatment of AML patients.

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Purpose Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC. Methods The expression levels of the β 2 -adrenergic receptor (β 2 -AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β 2 -AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β 2 -AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis. Results The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β 2 -AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the co-culture assay, the sympathetic adrenergic NE/β 2 -AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth. Conclusion These results suggest that NE/β 2 -AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.

BackgroundRecent evidence suggests that there is a link between irritable bowel syndrome (IBS) and microbiota in the gut. The onset and maintenance of IBS may be caused by gut microbiota, but the causes of the pathophysiology of this disorder are unknown.Method25 patients who fulfilled Rome III criteria for IBS and 29 age- and gender-matched healthy controls were chosen in this study. The total bacterial DNA isolated from the two populations was investigated through amplicon pyrosequencing of the V3–V4 regions of the 16S ribosomal RNA gene.ResultsThe composition of bacteria in the groups differed between healthy controls and IBS subgroups from phylum to the genus level. Synergistetes phylum (p=0.016), Bacilli class (p=0.006), Lactobacillales order (p=0.006), Enterobacteriales order (p=0.02), the families Streptococcaceae (p=0.009), Enterobacteriaceae (p=0.02), and Enterococcaceae (p=0.001), and the genera Streptococcus (p=0.002), Enterobacter (p=0), Klebsiella (p=0.006), and Enterococcus (p=0.001) exhibited higher levels in IBS patients compared with healthy controls. By contrast, Clostridia class (p=0.024), Betaproteobacteria class (p=0.019), Clostridiales order (p=0.024), the families Bacteroidaceae (p=0.049), Desulfovibrionaceae (p<<0.01), and Lachnospiraceae (p=0.012), and the genera Bacteroides (p=0.049) and Roseburia (p=0.012) had lower levels in IBS patients. The genera Turicibacter and Collinsella were most abundant in 51–60 year old patients, followed by 31–40 year old IBS patients. We also detected Acinetobacter and Campylobacter belonging to Proteobacteria phylum in female IBS patients, but not in male patients.ConclusionThere were differences in faecal microbiota between IBS patients and healthy controls. The faecal microbiota of patients with IBS is associated with significant increases in detrimental and decreases in beneficial bacterial groups.AcknowledgmentSupported by grants from National Program on Key Basic Research Project (973 Program, 2013CB531405), and the National Natural Science Foundation of China (NSFC, No. 81641029 and 81370113).