BackgroundReprogrammed energy metabolism as an emerging hallmark of cancer has recently drawn special attention since it facilitate cell growth and proliferation. Recently, long noncoding RNAs (lncRNAs) have been served as key regulators implicated in tumor development and progression by promoting proliferation, invasion and metastasis. However, the associations of lncRNAs with cellular energy metabolism in lung cancer (LC) need to be clarified.MethodsHere, we conducted bioinformatics analysis and found insulin-like growth factor binding protein 4–1 (IGFBP4–1) as a new candidate lncRNA located in the upstream region of IGFBP4 gene. The expression levels of lnc-IGFBP4–1, mRNA levels of IGFBP4 in 159 paired lung cancer samples and adjacent, histological normal tissues by qRT-PCR. Over-expression and RNA interference (RNAi) approaches were adopted to investigate the biological functions of lnc-IGFBP4–1. The intracellular ATP level was measured using the Cell Titer-Glo Luminescent Cell Viability Assay kit, and changes in metabolic enzymes were examined in cancer cells and normal pulmonary epithelial cells with qRT-PCR.ResultsOur results showed that lnc-IGFBP4–1 was significantly up-regulated in LC tissues compared with corresponding non-tumor tissues (P < 0.01), and its expression level was significantly correlated with TNM stage (P < 0.01) and lymph node metastasis (P < 0.05). Further investigation showed that overexpression of lnc-IGFBP4–1 significantly promoted LC cell proliferation in vitro and in vivo, while downregulation of endogenous lnc-IGFBP4–1 could inhibited cell proliferation and induce apoptosis. Moreover, we found lnc-IGFBP4–1 could influences ATP production levels and expression of enzymes including HK2, PDK1 and LDHA, in addition, decline in both ATP production and these enzymes in response to 2-DG and 2-DG-combined Rho123, respectively, was observed in lnc-IGFBP4–1-overespressing LC cells, indicative of an enhanced aerobic glycolysis rate. Finally, lnc-IGFBP4–1 was observed to negatively correlate with gene IGFBP4, and lower expression level of IGFPB4 was found after lnc-IGFBP4–1-overexpression was transfected into PC9 cells, higher expression level of IGFPB4 was also found after lnc-IGFBP4–1-downregulation was transfected into GLC-82 cells, which indicates that IGFBP4 may exert its targeting function regulated by lnc-IGFBP4–1.ConclusionsTaken together, these findings provide the first evidence that lnc-IGFBP4–1 is significantly up-regulated in LC tissues and plays a positive role in cell proliferation and metastasis through possible mechanism of reprogramming tumor cell energy metabolism, which suggests that lnc-IGFBP4–1 may be a promising biomarker in LC development and progression and as a potential therapeutic target for LC intervention.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0722-8) contains supplementary material, which is available to authorized users.

Plant pathogen effectors can recruit the host post-translational machinery to mediate their post-translational modification (PTM) and regulate their activity to facilitate parasitism, but few studies have focused on this phenomenon in the field of plant-parasitic nematodes. In this study, we show that the plant-parasitic nematode Meloidogyne graminicola has evolved a novel effector, MgGPP, that is exclusively expressed within the nematode subventral esophageal gland cells and up-regulated in the early parasitic stage of M. graminicola. The effector MgGPP plays a role in nematode parasitism. Transgenic rice lines expressing MgGPP become significantly more susceptible to M. graminicola infection than wild-type control plants, and conversely, in planta, the silencing of MgGPP through RNAi technology substantially increases the resistance of rice to M. graminicola. Significantly, we show that MgGPP is secreted into host plants and targeted to the ER, where the N-glycosylation and C-terminal proteolysis of MgGPP occur. C-terminal proteolysis promotes MgGPP to leave the ER, after which it is transported to the nucleus. In addition, N-glycosylation of MgGPP is required for suppressing the host response. The research data provide an intriguing example of in planta glycosylation in concert with proteolysis of a pathogen effector, which depict a novel mechanism by which parasitic nematodes could subjugate plant immunity and promote parasitism and may present a promising target for developing new strategies against nematode infections.

Meloidogyne enterolobii is one of the most important plant-parasitic nematodes that can overcome the Mi-1 resistance gene and damage many economically important crops. Translationally controlled tumour protein (TCTP) is a multifunctional protein that exists in various eukaryotes and plays an important role in parasitism. In this study, a novel M. enterolobii TCTP effector, named MeTCTP, was identified and functionally characterized. MeTCTP was specifically expressed within the dorsal gland and was up-regulated during M. enterolobii parasitism. Transient expression of MeTCTP in protoplasts from tomato roots showed that MeTCTP was localized in the cytoplasm of the host cells. Transgenic Arabidopsis thaliana plants overexpressing MeTCTP were more susceptible to M. enterolobii infection than wild-type plants in a dose-dependent manner. By contrast, in planta RNA interference (RNAi) targeting MeTCTP suppressed the expression of MeTCTP in infecting nematodes and attenuated their parasitism. Furthermore, MeTCTP could suppress programmed cell death triggered by the pro-apoptotic protein BAX. These results demonstrate that MeTCTP is a novel plant-parasitic nematode effector that promotes parasitism, probably by suppressing programmed cell death in host plants.

Schistosoma japonicum ( S. japonicum ) is one of the etiological agents of schistosomiasis, a widespread zoonotic parasitic disease. However, the mechanism of the balanced co-existence between the host immune system and S. japonicum as well as their complex interaction remains unclear. In this study, 16S rRNA gene sequencing, combined with metagenomic sequencing approach as well as ultraperformance liquid chromatography–mass spectrometry metabolic profiling, was applied to demonstrate changes in the gut microbiome community structure during schistosomiasis progression, the functional interactions between the gut bacteria and S. japonicum infection in BALB/c mice, and the dynamic metabolite changes of the host. The results showed that both gut microbiome and the metabolites were significantly altered at different time points after the infection. Decrease in richness and diversity as well as differed composition of the gut microbiota was observed in the infected status when compared with the uninfected status. At the phylum level, the gut microbial communities in all samples were dominated by Firmicutes, Bacteroidetes, Proteobacteria, and Deferribacteres, while at the genus level, Lactobacillus, Lachnospiraceae NK4A136 group, Bacteroides, Staphylococcus , and Alloprevotella were the most abundant. After exposure, Roseburia , and Ruminococcaceae UCG-014 decreased, while Staphylococcus, Alistipes , and Parabacteroides increased, which could raise the risk of infections. Furthermore, LEfSe demonstrated several bacterial taxa that could discriminate between each time point of S. japonicum infection. Besides that, metagenomic analysis illuminated that the AMP-activated protein kinase (AMPK) signaling pathway and the chemokine signaling pathway were significantly perturbed after the infection. Phosphatidylcholine and colfosceril palmitate in serum as well as xanthurenic acid, naphthalenesulfonic acid, and pimelylcarnitine in urine might be metabolic biomarkers due to their promising diagnostic potential at the early stage of the infection. Alterations of glycerophospholipid and purine metabolism were also discovered in the infection. The present study might provide further understanding of the mechanisms during schistosome infection in aspects of gut microbiome and metabolites, and facilitate the discovery of new targets for early diagnosis and prognostic purposes. Further validations of potential biomarkers in human populations are necessary, and the exploration of interactions among S. japonicum , gut microbiome, and metabolites is to be deepened in the future.

MicroRNAs, which serve as post-transcriptional modulators of numerous genes, have been found to be important regulators during the pathogenesis of osteosarcoma. This study demonstrates for the first time that microRNA-130a (miR-130a) is significantly upregulated in osteosarcoma, and associated with the metastasis of osteosarcoma. Elevated level of miR-130a was closely correlated with poor clinical features and prognosis of osteosarcoma patients. In vitro assays revealed that miR-130a could potentiate the migration, invasion and the epithelial-mesenchymal transtion (EMT) of osteosarcoma cells. Moreover, phosphatase and tensin homolog (PTEN) was confirmed as not only a direct downstream target but also a functional mediator of miR-130a. MiR-130a exerted promoting effects on metastatic behavior and EMT of osteosarcoma cells through suppressing PTEN expression. Based on these findings, we conclude that miR-130a is a promising prognostic biomarker for osteosarcoma patients, and targeting miR-130a may be a potential treatment option for osteosarcoma patients with metastasis.