The accurate control of cell proliferation and survival is critical for animal development. The Hippo tumor suppressor pathway regulates both of these parameters by controlling the nuclear availability of the transcriptional coactivator Yorkie (Yki), which regulates downstream target genes together with Scalloped (Sd), a DNA-binding protein. Here we provide evidence that Yki can also regulate target genes in conjunction with Homothorax (Hth) and Teashirt (Tsh), two DNA-binding transcription factors expressed in the uncommitted progenitor cells of the Drosophila eye imaginal disc. Clonal analyses demonstrate that Hth and Tsh promote cell proliferation and protect eye progenitor cells from apoptosis. Genetic epistasis experiments suggest that Hth and Tsh execute these functions with Yki, in part by up-regulating the microRNA bantam. A physical interaction between Hth and Yki can be detected in cell culture, and we show that Hth and Yki are bound to a DNA sequence ;14 kb upstream of the bantam hairpin in eye imaginal disc cells, arguing that this regulation is direct. These data suggest that the Hippo pathway uses different DNA-binding transcription factors depending on the cellular context. In the eye disc, Hth and Tsh provide spatial information to this pathway, promoting cell proliferation and survival in the progenitor domain.[Keywords: Drosophila eye development; Hippo signaling pathway; Homothorax; Yorkie; apoptosis; cell proliferation] Supplemental material is available at http://www.genesdev.org.

Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer specific lncRNAs in lncRNA-related ceRNA network of lung adenocarcinoma (LUAD) are still unclear. In the present study, the 465 RNA sequencing profiles in LUAD patients were obtained from the cancer genome atlas (TCGA) database, which provides large sample RNA sequencing data free of charge, and 41 cancer specific lncRNAs, 25 miRNAs and 1053 mRNAs (fold change >2, p<0.05) were identified. Then, the lncRNA-miRNA-mRNA ceRNA network of LUAD was constructed with 29 key lncRNAs, 24 miRNAs and 72 mRNAs. Subsequently, we selected these 29 key lncRNAs to analyze their correlation with clinical features, and 21 of them were aberrantly expressed with tumor pathological stage, TNM staging system, lymph node metastasis and patient outcome assessment, respectively. Furthermore, there were 5 lncRNAs (BCRP3, LINC00472, CHIAP2, BMS1P20 and UNQ6494) positively correlated with overall survival (OS, log-rank p<0.05). Finally, 7 cancer specific lncRNAs were randomly selected to verify the expression in 53 newly diagnosed LUAD patients using qRT-PCR. The expression results between TCGA and qRT-PCR were 100% in agreement. The correlation between AFAP1-AS1 and LINC00472 and clinical features were also confirmed. Thus, our results showed the lncRNA expression profiles and we constructed an lncRNA-miRNA-mRNA ceRNA network in LUAD. The present study provides novel insight for better understanding of lncRNA-related ceRNA network in LUAD and facilitates the identification of potential biomarkers for diagnosis and prognosis.

Abstract. Abnormal expression of long non-coding RNAs (lncRNAs) have been shown to play an important role in tumor biology. The Cancer Genome Atlas (TCGA) platform is a large sample sequencing database of lncRNAs, and further analysis of the associations between these data and patients' clinical related information can provide new approaches to find the functions of lncRNA. In the present study, 361 RNA sequencing profiles of gastric cancer (GC) patients were selected from TCGA. Then, we constructed the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network of GC. There were 25 GC specific lncRNAs (fold change >2, p<0.05) identified, 19 of them were included in ceRNA network. Subsequently, we selected these 19 key lncRNAs and analyzed the correlations with clinical features and overall survival, 14 of them were discriminatively expressed with tumor size, tumor grade, TNM stage and lymphatic metastasis (p<0.05). In addition, eight lncRNAs (RPLP0P2, FOXD2-AS1, H19, TINCR, SLC26A4-AS1, SMIM10L2A, SMIM10L2B and SNORD116-4) were found to be significantly associated with overall survival (log-rank p<0.05). Finally, two key lncRNAs HOTAIR and UCA1 were selected for validation of their expression levels in 82 newly diagnosed GC patients by qRT-PCR. Results showed that the fold changes between TCGA and qRT-PCR were 100% in agreement. In addition, we also found that HOTAIR was significantly correlated with tumor size and lymphatic metastasis (p<0.05), and UCA1 was significantly correlated with tumor size, TNM stage and lymphatic metastasis (p<0.05).The clinical relevance of the two lncRNAs and the bioinformatics analysis results were almost the same. Overall, our study showed the GC specific lncRNAs expression patterns and a ceRNA network in GC. Clinical features related to GC specific lncRNAs also suggested these lncRNAs are worthwhile for further study as novel candidate biomarkers for the clinical diagnosis of GC and potential indicators for prognosis. IntroductionNoncoding RNAs (ncRNAs) are transcripts that have no ability of coding proteins, which widely exit in high eukaryotics. According to their characteristics, ncRNAs can be divided into several subtypes including transfer RNA, small nucleolar RNA (snoRNA), ribosomal RNA (rRNA), microRNA (miRNA) and long non-coding RNA (lncRNA). The amount of the ncRNAs transcripts is >98% of the whole genome transcripts and have been suggested to represent transcriptional noise (1). However, more and more evidence indicates that transcriptional output of genome is far more complex than predicted, and suggests new paradigms of ncRNA regulation (2).Recent studies suggest that the ncRNAs may play important biological roles in transcriptional regulation, cellular development, formation of chromosome and RNA modification (3). Based on the transcript size, ncRNAs are grouped into small ncRNAs (<200 bp) and long ncRNAs (>200 bp, up to 100 kb). lncRNA is the functional end-product, and the level of lncRNA expression correlates directly with the level of the active molecule. Thus, ...

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Plant hormones are a class of organic substances which are synthesized during the plant metabolism. They have obvious physiological effect on plant growth at very low concentrations. Generally, plant hormones are mainly divided into 5 categories: auxins, cytokinins, ethylene, gibberellins (GAs) and abscisic acid (ABA). With the deepening of research, some novel plant hormones such as brassinosteroid and salicylates have been found and identified. The plant hormone products are mainly obtained through plant extraction, chemical synthesis as well as microbial fermentation. However, the extremely low yield in plants and relatively complex chemical structure limit the development of the former 2 approaches. Therefore, more attention has been paid into the microbial fermentative production. In this commentary, the developments and technological achievements of the 2 important plant hormones (GAs and ABA) have been discussed. The discovery, producing strains, fermentation technologies, and their accumulation mechanisms are first introduced. Furthermore, progresses in the industrial mass scale production are discussed. Finally, guidelines for future studies for GAs and ABA production are proposed in light of the current progress, challenges and trends in the field. With the widespread use of plant hormones in agriculture, we believe that the microbial production of plant hormones will have a bright future.

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The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated during disease occurrence and to play an important role in the progression of several cancers. However, the biological role and potential regulation mechanism of UCA1 in the carcinogenesis of gastric cancer remain unclear. In the present study, we found that UCA1 was aberrantly upregulated in gastric cancer tissues and gastric cancer cell lines, and was associated with TNM stage and metastasis. UCA1 silencing significantly inhibited gastric cancer BGC-823 cell proliferation and increased its apoptosis. We also found that UCA1 played an important role in the migration and invasion of gastric cancer cells in vitro and in vivo. The molecular mechanism of UCA1 suggested that UCA1 regulates the PI3K-Akt-mTOR signaling proteins and their downstream mediators, to alter gastric cancer progression in vitro and in vivo. Collectively, the results showed a pivotal role of UCA1 in the tumorigenesis of gastric cancer. In addition, the study characterized a novel lncRNA-mRNA regulatory network, which may lead to a better understanding of the pathogenesis of gastric cancer and assist in lncRNA-directed diagnosis and therapy for this malignancy.

These key miRNAs may functions as potential candidate biomarkers for the clinical diagnosis, classification and prognosis for GC.