Tumor-associated macrophages have important roles in hepatocellular carcinoma (HCC) initiation and progression. Long noncoding RNAs(lncRNAs) have also been reported to be involved in HCC. In this study, we explored how lncRNA LINC00662 may influence HCC progression through both tumor cell-dependent and macrophage-dependent mechanisms. LINC00662 was found to be upregulated in HCC, and high LINC00662 levels correlated with poor survival of HCC patients. LINC00662 upregulated WNT3A expression and secretion via competitively binding miR-15a, miR-16, and miR-107. Through inducing WNT3A secretion, LINC00662 activated Wnt/b-catenin signaling in HCC cells in an autocrine manner and further promoted HCC cell proliferation, cell cycle, and tumor cell invasion, while repressing HCC cell apoptosis. In addition, acting through WNT3A secretion, LINC00662 activated Wnt/b-catenin signaling in macrophages in a paracrine manner and further promoted M2 macrophage polarization. Via activating Wnt/b-catenin signaling and M2 macrophages polarization, LINC00662 significantly promoted HCC tumor growth and metastasis in vivo. Hence, targeting LINC00662 may provide novel therapeutic strategy against HCC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68, 394-424. Budhu A, Forgues M, Ye QH, Jia HL, He P, Zanetti KA, Kammula US, Chen Y, Qin LX, Tang ZY et al. (2006) Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell 10, 99-111. Carlson P, Dasgupta A, Grzelak CA, Kim J, Barrett A, Coleman IM, Shor RE, Goddard ET, Dai J, Schweitzer EM et al. (2019) Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy. Nat Cell Biol 21, 238-250. Cassetta L, Fragkogianni S, Sims AH, Swierczak A, Forrester LM, Zhang H, Soong DYH, Cotechini T, Anur P, Lin EY et al. (2019) Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers, and therapeutic targets. Cancer Cell 35, 588-602 e510. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A and Bozzoni I (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147, 358-369. Chandradoss SD, Schirle NT, Szczepaniak M, MacRae IJ and Joo C (2015) A dynamic search process underlies microRNA targeting. Cell 162, 96-107. PP et al. (2019a) Extracellular vesicle-packaged HIF-1alpha-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol 21, 498-510. X et al. (2019b) TNF-alpha derived from M2 tumor-asso...

Compared to mono-species biofilm, biofilms formed by cross-kingdom pathogens are more refractory to conventional antibiotics, thus complicating clinical treatment and causing significant morbidity. Lemongrass essential oil and its bioactive component citral were previously demonstrated to possess strong antimicrobial efficacy against pathogenic bacteria and fungi. However, their effects on polymicrobial biofilms remain to be determined. In this study, the efficacy of lemongrass (Cymbopogon flexuosus) essential oil and its bioactive part citral against dual-species biofilms formed by Staphylococcus aureus and Candida species was evaluated in vitro. Biofilm staining and viability test showed both lemongrass essential oil and citral were able to reduce biofilm biomass and cell viability of each species in the biofilm. Microscopic examinations showed these agents interfered with adhesive characteristics of each species and disrupted biofilm matrix through counteracting nucleic acids, proteins and carbohydrates in the biofilm. Moreover, transcriptional analyses indicated citral downregulated hyphal adhesins and virulent factors of Candida albicans, while also reducing expression of genes involved in quorum sensing, peptidoglycan and fatty acids biosynthesis of S. aureus. Taken together, our results demonstrate the potential of lemongrass essential oil and citral as promising agents against polymicrobial biofilms as well as the underlying mechanisms of their activity in this setting.

A core component of the α-proteobacterial general stress response (GSR) is the extracytoplasmic function (ECF) sigma factor EcfG, exclusively present in this taxonomic class. Half of the completed α-proteobacterial genome sequences contain two or more copies of genes encoding σEcfG-like sigma factors, with the primary copy typically located adjacent to genes coding for a cognate anti-sigma factor (NepR) and two-component response regulator (PhyR). So far, the widespread occurrence of additional, non-canonical σEcfG copies has not satisfactorily been explained. This study explores the hierarchical relation between Rhizobium etli σEcfG1 and σEcfG2, canonical and non-canonical σEcfG proteins, respectively. Contrary to reports in other species, we find that σEcfG1 and σEcfG2 act in parallel, as nodes of a complex regulatory network, rather than in series, as elements of a linear regulatory cascade. We demonstrate that both sigma factors control unique yet also shared target genes, corroborating phenotypic evidence. σEcfG1 drives expression of rpoH2, explaining the increased heat sensitivity of an ecfG1 mutant, while katG is under control of σEcfG2, accounting for reduced oxidative stress resistance of an ecfG2 mutant. We also identify non-coding RNA genes as novel σEcfG targets. We propose a modified model for GSR regulation in R. etli, in which σEcfG1 and σEcfG2 function largely independently. Based on a phylogenetic analysis and considering the prevalence of α-proteobacterial genomes with multiple σEcfG copies, this model may also be applicable to numerous other species.