Nuclear receptors regulate gene expression in response to environmental cues, but the molecular events governing the cell-type specificity of nuclear receptors remain poorly understood. Here we outline a role for a non-coding RNA in modulating the cell type-specific actions of LXRs, sterol-activated nuclear receptors that regulate the expression of genes involved in cholesterol homeostasis and that have been causally linked to the pathogenesis of atherosclerosis. We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the critical cholesterol efflux gene Abca1. Mice lacking the MeXis gene show reduced Abca1 expression in a tissue-selective manner. Furthermore, loss of MeXis in mouse bone marrow cells alters chromosome architecture at the Abca1 locus, impairs cellular responses to cholesterol overload, and accelerates the development of atherosclerosis. Mechanistic studies reveal that MeXis interacts with and guides promoter binding of the transcriptional coactivator DDX17. The identification of MeXis as a lncRNA modulator of LXR-dependent gene expression expands our understanding of the mechanisms underlying cell-type selective actions of nuclear receptors in physiology and disease.

Strand-selection is the final step of microRNA biogenesis in which functional mature miRNAs are generated from one or both arms of precursor. The preference of strand-selection is diverse during development and tissue formation, however, its pathological effect is still unknown. Here we find that two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, are inversely expressed and play exactly opposite roles in gastric cancer progression. Higher-5p with lower-3p expression pattern is significantly correlated with higher TNM stages and poor prognosis of gastric cancer patients. The increase of miR-574-5p/-3p ratio, named miR-574 arm-imbalance is partially due to the dynamic expression of their highly complementary targets in gastric carcinogenesis, moreover, the arm-imbalance of miR-574 is in turn involved and further promotes gastric cancer progression. Our results indicate that miR-574 arm-imbalance contribute to gastric cancer progression and re-modification of the miR-574-targets homeostasis may represent a promising strategy for gastric cancer therapy.

Chemotherapy has improved the survival of patients with gastric cancer by unknown mechanisms. In this study, we showed that cisplatin and docetaxel used in gastric cancer treatment increase the expression of miRNA-29 (miR-29) family members and decrease the expression of their oncogenic targets, mediating a significant part of the efficacious benefits of these chemotherapeutic agents. In particular, patients with gastric cancer who experienced recurrences after chemotherapy tended to exhibit low levels of miR-29c expression in their tumors, suggesting that miR29c activation may contribute to the chemotherapeutic efficacy.

Atherosclerosis is a complex and chronic disease characterized by lipid deposition in the vessel wall that leads to an inflammatory and proliferative cascade involving smooth muscle, endothelial and immune cells. Despite substantial improvements in our understanding of mechanisms contributing to atherosclerosis and overall reduction in cardiovascular mortality, the absolute disease burden remains substantially high. The recent discovery of a new group of mediators known as long noncoding RNAs (lncRNAs) offers a unique opportunity for the development of novel diagnostic and therapeutic tools in atherothrombotic disease. A number of studies suggest that lncRNAs are important mediators in health and disease and rapidly accumulating evidence implicates lncRNAs in regulatory circuits controlling atherosclerosis. In this review, we outline important contributions of lncRNAs to atherosclerosis and its associated risk factors including hypercholesterolemia, diabetes, hypertension and obesity.

BackgroundThe migratory locust, Locusta migratoria manilensis, is an immensely destructive agricultural pest that forms a devastating and voracious gregarious phase. The fungal insect pathogen, Metarhizium acridum, is a specialized locust pathogen that has been used as a potent mycoinsecticide for locust control. Little, however, is known about locust immune tissue, i.e. fat body and hemocyte, responses to challenge by this fungus.MethodsRNA-seq (RNA sequencing) technology were applied to comparatively examine the different roles of locust fat body and hemocytes, the two major contributors to the insect immune response, in defense against M. acridum. According to the sequence identity to homologies of other species explored immune response genes, immune related unigenes were screened in all transcriptome wide range from locust and the differential expressed genes were identified in these two tissues, respectively.ResultsAnalysis of differentially expressed locust genes revealed 4660 and 138 up-regulated, and 1647 and 23 down-regulated transcripts in the fat body and hemocytes, respectively after inoculation with M. acridum spores. GO (Gene Ontology) enrichment analysis showed membrane biogenesis related proteins and effector proteins significantly differentially expressed in hemocytes, while the expression of energy metabolism and development related transcripts were enriched in the fat body after fungal infection. A total of 470 immune related unigenes were identified, including members of the three major insect immune pathways, i.e. Toll, Imd (immune deficiency) and JAK/STAT (janus kinase/signal transduction and activator of transcription). Of these, 58 and three were differentially expressed in the insect fat body or hemocytes after infection, respectively. Of differential expressed transcripts post challenge, 43 were found in both the fat body and hemocytes, including the LmLys4 lysozyme, representing a microbial cell wall targeting enzyme.ConclusionsThese data indicate that locust fat body and hemocytes adopt different strategies in response to M. acridum infection. Fat body gene expression after M. acridum challenge appears to function mainly through activation of innate immune related genes, energy metabolism and development related genes. Hemocyte responses attempt to limit fungal infection primarily through regulation of membrane related genes and activation of cellular immune responses and release of humoral immune factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2089-9) contains supplementary material, which is available to authorized users.