Identification of genes underlying phenotypic plasticity of wing size via insulin signaling pathway by network-based analysis in Sogatella furcifera.

BACKGROUND: Phenotypic plasticity is a common and highly adaptive phenomenon where the same genotype produces different phenotypes in response to environmental cues. Sogatella furcifera, a migratory pest of rice exhibits wing dimorphism, is a model insect for studying phenotypic plasticity of wing size. The Insullin-PI3K-Akt-FOXO signaling pathway plays a crucial role in the manipulation of wing size in the migratory insects. However, the regulatory mechanism via the pathway involved in wing dimorphism are still unexplored. RESULTS: Accompanied by special alternative splicing, genes involved in muscle contraction and energy metabolism were highly expressed in the wing hinges of macropters, demonstrating their adaptation for energy-demanding long-distance flights. Based on FOXO ChIP-Seq analysis, a total of 1259 putative target genes were observed in the wing hinges, including wing morph development, flight muscle and energy metabolism genes. An integrated gene interaction network was built by combining four heterogeneous datasets, and the IIS-PI3K-Akt-FOXO pathway was clustered in a divided functional module. In total, 45 genes in the module directly interacting with the IIS-PI3K-Akt-FOXO pathway showed differential expression levels between the two wing hinges, thus are regarded as potential Insulin pathway mediated wing dimorphism related genes (IWDRGs). Of the 45 IWDRGs, 5 were selected for verification by gene knockdown experiments, and played significant roles in the insect wing size regulation. CONCLUSIONS: We provided valuable insights on the genetic basis of wing dimorphism, and also demonstrated that network analysis is a powerful approach to identify new genes regulating wing dimorphic development via insulin signaling pathway in the migratory insect.

Bacterial endosymbiont Cardinium cSfur genome sequence provides insights for understanding the symbiotic relationship in Sogatella furcifera host.

BACKGROUND: Sogatella furcifera is a migratory pest that damages rice plants and causes severe economic losses. Due to its ability to annually migrate long distances, S. furcifera has emerged as a major pest of rice in several Asian countries. Symbiotic relationships of inherited bacteria with terrestrial arthropods have significant implications. The genus Cardinium is present in many types of arthropods, where it influences some host characteristics. We present a report of a newly identified strain of the bacterial endosymbiont Cardinium cSfur in S. furcifera. RESULT: From the whole genome of S. furcifera previously sequenced by our laboratory, we assembled the whole genome sequence of Cardinium cSfur. The sequence comprised 1,103,593 bp with a GC content of 39.2%. The phylogenetic tree of the Bacteroides phylum to which Cardinium cSfur belongs suggests that Cardinium cSfur is closely related to the other strains (Cardinium cBtQ1 and cEper1) that are members of the Amoebophilaceae family. Genome comparison between the host-dependent endosymbiont including Cardinium cSfur and free-living bacteria revealed that the endosymbiont has a smaller genome size and lower GC content, and has lost some genes related to metabolism because of its special environment, which is similar to the genome pattern observed in other insect symbionts. Cardinium cSfur has limited metabolic capability, which makes it less contributive to metabolic and biosynthetic processes in its host. From our findings, we inferred that, to compensate for its limited metabolic capability, Cardinium cSfur harbors a relatively high proportion of transport proteins, which might act as the hub between it and its host. With its acquisition of the whole operon related to biotin synthesis and glycolysis related genes through HGT event, Cardinium cSfur seems to be undergoing changes while establishing a symbiotic relationship with its host. CONCLUSION: A novel bacterial endosymbiont strain (Cardinium cSfur) has been discovered. A genomic analysis of the endosymbiont in S. furcifera suggests that its genome has undergone certain changes to facilitate its settlement in the host. The envisaged potential reproduction manipulative ability of the new endosymbiont strain in its S. furcifera host has vital implications in designing eco-friendly approaches to combat the insect pest.

Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis.

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related mortality worldwide. Immunotherapy offers promising new treatment options for gastric cancer patients; however, it is only effective in a limited fraction of patients. In this study, we evaluated the composition of 22 tumor-infiltrating lymphocytes (TILs) in TCGA Stomach Adenocarcinoma (STAD) using deconvolution-based method by analyzing the publicly available bulk tumor RNA-seq data. The patients were classified into high-TIL and low-TIL subtypes based on their immune cell profiles and prognosis outputs. The differentially expressed genes (DEGs) between the two subtypes were identified, and GO/KEGG analysis showed that broad immune genes, such as PD-L1 and PD-1, were highly expressed in the high-TIL subtype. A comprehensive protein-protein interaction (PPI) network centered on DEGs was built, and 16 hub genes of the network were further identified. Based on the hub genes, an elastic model with 11 gene signatures (NKG7, GZMB, IL2RB, CCL5, CD8A, IDO1, MYH1, GNLY, CXCL11, GBP5 and PRF1) was developed to predict the high-TIL subtype. In summary, our findings showed that the compositions of TILs within the tumor immune microenvironment of stomach cancer patients are highly heterogeneous, and the profiles of TILs have the potential to be predictive markers of patients' responses and overall survival outcomes.

Exploration of the genomic landscape of a long-term surviving stage III colorectal cancer patient identifies recurrent and rare mutations: a case report.

A 40-year old female patient from the Chinese Han population presented colorectal cancer (CRC) related symptoms including abdominal discomfort, tenesmus and severe back pain, and was admitted to the First Affiliated Anhui Medical University in October, 2008. The size of her tumor was 3 cm × 3 cm, and the carcinoma had invaded the serosa layer, covering 3/4 of the intestine tube. She was diagnosed with stage III CRC after examination. The patient presented a good prognosis with over 8-year survival after curative surgery and adjuvant therapy with Oxaliplatin and Huaier granules, a traditional Chinese medicine. Using the whole-genome sequencing (WGS) data, we profiled the germline and somatic mutations and obtained an all-inclusive data of the genomic alterations. The genomic alterations were compared with those of stage III CRC patients in The Cancer Genome Atlas Network (TCGA). Mutations in APC, TP53, KRAS, SMAD4, FBXW7 and PIK3CA defined as drivers in TCGA patients were not recorded in our study. However, mutations in MUC4, MUC16, ARID1B, BAZ1A, BRCA2, CTNND1 and NCOA2 rarely reported in TCGA patients were predominant in our patient. Additionally, we observed loss of heterozygosity (LOH) in POLE, RET, BMPR1A, NCOA4 and 30 other genes in contrast to deletion and amplification events recorded in TCGA patients. Overall, we produced a genomic mutation profile of a long-term surviving CRC patient and identified recurrent and rare mutations that could provide a valuable resource for further study into the alterations that characterize advanced CRC which may be useful to design clinical therapy for personalized medicine.

Genome-wide characterization and developmental expression profiling of long non-coding RNAs in Sogatella furcifera.

The genome-wide characterization of long non-coding RNA (lncRNA) in insects demonstrates their importance in fundamental biological processes. Essentially, an in-depth understanding of the functional repertoire of lncRNA in insects is pivotal to insect resources utilization and sustainable pest control. Using a custom bioinformatics pipeline, we identified 1861 lncRNAs encoded by 1852 loci in the Sogatella furcifera genome. We profiled lncRNA expression in different developmental stages and observed that the expression of lncRNAs is more highly temporally restricted compared to protein-coding genes. More up-regulated Sogatella furcifera lncRNA expressed in the embryo, 4th and 5th instars, suggesting that increased lncRNA levels may play a role in these developmental stages. We compared the relationship between the expression of Sogatella furcifera lncRNA and its nearest protein gene and found that lncRNAs were more correlated to their downstream coding neighbors on the opposite strand. Our genome-wide profiling of lncRNAs in Sogatella furcifera identifies exciting candidates for characterization of lncRNAs, and also provides information on lncRNA regulation during insect development.

Integrated analysis of whole genome and transcriptome sequencing in a young patient with gastric cancer provides insights for precision therapy.

Gastric cancer is a leading cause of cancer-associated deaths worldwide and is considered to be an age-related disease. In younger patients, gastric cancer is biologically more aggressive, and prognosis is worse compared with that in elderly patients. In the present case report, the whole genome and transcriptome was sequenced in a 26-year-old patient with gastric cancer who presented with gastric cancer-related symptoms and was admitted to the First Affiliated Anhui Medical Hospital (Hefei, China) in December 2016. In total, 9 germline and 4 somatic mutations were identified in the patient, and there were more deleterious sites in the germline mutated genes. Genes with somatic mutations, such as MUC2, MUC4, SLC8A2, and with structural variations, including CCND3, FGFR2 and FGFR3, were found to be differentially expressed. Cancer-associated pathways, such as the 'calcium signaling pathway', 'cGMP-PKG signaling pathway' and 'transcriptional mis-regulation' were also enriched at both the genomic and transcriptomic levels. The genes found to have germline (SFRP4), somatic (MUC2, MUC4, SLC8A2) mutations, or structural variations (CCND3, FGFR2 and FGFR3) were differentially expressed in the patient and could be promising precision therapy targets.

lncRNA Sensing of a Viral Suppressor of RNAi Activates Non-canonical Innate Immune Signaling in Drosophila.

Antiviral immunity in insects is mediated by the RNA interference (RNAi) pathway. Viruses evade antiviral RNAi by expressing virulence factors known as viral suppressors of RNAi (VSR). Here, we report the identification of VINR, a Drosophila VSR-interacting long non-coding (lnc) RNA that activates non-canonical innate immune signaling upon detection of the dsRNA-binding VSR of Drosophila C virus (DCV). VINR is required for the induction of antimicrobial peptide (AMP) genes but dispensable for antiviral RNAi. VINR functions by preventing the ubiquitin proteasome-dependent degradation of Cactin, a coiled-coil and arginine-serine-rich domain-containing protein that regulates a non-cannonical antimicrobial pathway for AMP induction. CRISPR-Cas9 knockout of VINR in Drosophila cells enhances DCV replication independently of antiviral RNAi, and VINR-knockout adult flies exhibit enhanced disease susceptibility to DCV and bacteria. Our findings reveal a counter counter-defense strategy activated by a lncRNA in response to the viral suppression of the primary antiviral RNAi immunity.