We identified 21 genes overexpressed in ovarian cancer (OC) bowel metastases compared to primary tumors. • High expression of these genes in primary OCs is associated with a need of complex bowel surgery and poor prognosis.• These genes may help identify potential therapeutic targets of malignant bowel obstruction in OC. a b s t r a c tObjective. This study is designed to identify genes and pathways that could promote metastasis to the bowel in high-grade serous ovarian cancer (OC) and evaluate their associations with clinical outcomes.Methods. We performed RNA sequencing of OC primary tumors (PTs) and their corresponding bowel metastases (n = 21 discovery set; n = 18 replication set). Differentially expressed genes (DEGs) were those expressed at least 2-fold higher in bowel metastases (BMets) than PTs in at least 30% of patients (P b .05) with no increased expression in paired benign bowel tissue and were validated with quantitative reverse transcription PCR. Using an independent OC cohort (n = 333), associations between DEGs in PTs and surgical and clinical outcomes were performed. Immunohistochemistry and mouse xenograft studies were performed to confirm the role of LRRC15 in promoting metastasis.Results. Among 27 DEGs in the discovery set, 21 were confirmed in the replication set: SFRP2, Col11A1, LRRC15, ADAM12, ADAMTS12, MFAP5, LUM, PLPP4, FAP, POSTN, GRP, MMP11, MMP13, C1QTNF3, EPYC, DIO2, KCNA1, NETO1, NTM, MYH13, and PVALB. Higher expression of more than half of the genes in the PT was associated with an increased requirement for bowel resection at primary surgery and an inability to achieve complete cytoreduction. Increased expression of LRRC15 in BMets was confirmed by immunohistochemistry and knockdown of LRRC15 significantly inhibited tumor progression in mice.Conclusions. We identified 21 genes that are overexpressed in bowel metastases among patients with OC. Our findings will help select potential molecular targets for the prevention and treatment of malignant bowel obstruction in OC. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

BackgroundFNR homologues constitute an important class of transcription factors that control a wide range of anaerobic physiological functions in a number of bacterial species. Since FNR homologues are some of the most pervasive transcription factors, an understanding of their involvement in regulating anaerobic gene expression in different species sheds light on evolutionary similarity and differences. To address this question, we used a combination of high throughput RNA-Seq and ChIP-Seq analysis to define the extent of the FnrL regulon in Rhodobacter capsulatus and related our results to that of FnrL in Rhodobacter sphaeroides and FNR in Escherichia coli.ResultsOur RNA-seq results show that FnrL affects the expression of 807 genes, which accounts for over 20 % of the Rba. capsulatus genome. ChIP-seq results indicate that 42 of these genes are directly regulated by FnrL. Importantly, this includes genes involved in the synthesis of the anoxygenic photosystem. Similarly, FnrL in Rba. sphaeroides affects 24 % of its genome, however, only 171 genes are differentially expressed in common between two Rhodobacter species, suggesting significant divergence in regulation.ConclusionsWe show that FnrL in Rba. capsulatus activates photosynthesis while in Rba. sphaeroides FnrL regulation reported to involve repression of the photosystem. This analysis highlights important differences in transcriptional control of photosynthetic events and other metabolic processes controlled by FnrL orthologues in closely related Rhodobacter species. Furthermore, we also show that the E. coli FNR regulon has limited transcriptional overlap with the FnrL regulons from either Rhodobacter species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2162-4) contains supplementary material, which is available to authorized users.

Anoxygenicphotosynthetic prokaryotes have simplified photosystems that represent ancient lineages that predate the more complex oxygen evolving photosystems present in cyanobacteria and chloroplasts. These organisms thrive under illuminated anaerobic photosynthetic conditions, but also have the ability to grow under dark aerobic respiratory conditions. This study provides a detailed snapshot of transcription ground states of both dark aerobic and anaerobic photosynthetic growth modes in the purple photosynthetic bacterium Rhodobactercapsulatus. Using 18 biological replicates for aerobic and photosynthetic states, we observed that 1834 genes (53 % of the genome) exhibited altered expression between aerobic and anaerobic growth. In comparison with aerobically grown cells, photosynthetically grown anaerobic cells showed decreased transcription of genes for cobalamin biosynthesis (−45 %), iron transport and homeostasis (−42 %), motility (−32 %), and glycolysis (−34 %). Conversely and more intuitively, the expression of genes involved in carbon fixation (547 %), bacteriochlorophyll biosynthesis (162 %) and carotenogenesis (114 %) were induced. We also analysed the relative contributions of known global redox transcription factors RegA, FnrL and CrtJ in regulating aerobic and anaerobic growth. Approximately 50 % of differentially expressed genes (913 of 1834) were affected by a deletion of RegA, while 33 % (598 out of 1834) were affected by FnrL, and just 7 % (136 out of 1834) by CrtJ. Numerous genes were also shown to be controlled by more than one redox responding regulator.

CRP and FNR are well-characterized members of the CRP/FNR family of regulatory proteins that function to maximize cellular energy production. In this study, we identify several new subgroups of the CRP/FNR family, many of which have not yet been characterized.