Identification of Key lncRNAs Associated with Immune Infiltration and Prognosis in Gastric Cancer.

Long non-coding RNAs (lncRNAs), as promising novel biomarkers for cancer treatment and prognosis, can function as tumor suppressors and oncogenes in the occurrence and development of many types of cancer, including gastric cancer (GC). However, little is known about the complex regulatory system of lncRNAs in GC. In this study, we systematically analyzed lncRNA and miRNA transcriptomic profiles of GC based on bioinformatics methods and experimental validation. An lncRNA-miRNA interaction network related to GC was constructed, and the nine crucial lncRNAs were identified. These 9 lncRNAs were found to be associated with the prognosis of GC patients by Cox proportional hazards regression analysis. Among them, the expression of lncRNA SNHG14 can affect the survival of GC patients as a potential prognostic marker. Moreover, it was shown that SNHG14 was involved in immune-related pathways and significantly correlated with immune cell infiltration in GC. Meanwhile, we found that SNHG14 affected immune function in many cancers, such as breast cancer and esophageal carcinoma. Such information revealed that SNHG14 may serve as a potential target for cancer immunotherapy. As well, our study could provide practical and theoretical guiding significance for clinical application of non-coding RNAs.

A novel feedback regulated loop of circRRM2-IGF2BP1-MYC promotes breast cancer metastasis.

BACKGROUND: Metastasis is the leading cause of mortality in patients with breast cancer (BC). Studies demonstrate that circular RNAs (circRNAs) were involved in BC progression, while the molecular mechanisms remain largely unclear. METHODS: The microArray circRNA profiles were used to explore the differential expression circRNAs in BC and paracancerous normal tissues, and the quantitative reverse transcription-polymerase chain reaction was used to validate their expression level in clinical samples and cell lines. Nuclear/cytosolic fractionation and fluorescence in situ hybridization (FISH) assays were performed to examine circRRM2 (hsa_circ_0052582) subcellular location. The scratch wound healing and transwell assays were conducted to evaluate the impact of circRRM2 on BC cell migration and invasion. We predicted miRNAs that might bind with cricRRM2 and the downstream target genes using bioinformatics analysis and explored their expression levels and prognostic value in BC. FISH, RNA immunoprecipitation, Co-immunoprecipitation, Western blot, and rescue experiments were implemented to figure out circRRM2 function and underlying mechanisms in BC. RESULTS: The present study revealed several aberrant circRNAs in BC tissues and observed that circRRM2 was upregulated in tumor tissues of 40 patients with BC. High circRRM2 was significantly associated with advanced N stage in patients with BC. Gain- and loss- of function experiments revealed that circRRM2 promoted the migration and invasion of cells and functioned as an oncogene in BC. Mechanism studies showed that circRRM2 competed with miR-31-5p/miR-27b-3p to upregulate the IGF2BP1 expression. Furthermore, IGF2BP1 upregulated the circRRM2 level via interacting with MYC, which functioned as the transcriptional factor of circRRM2. Thus, the positive feedback loop that was composed of circRRM2/IGF2BP1/MYC was identified. CONCLUSION: This study confirms that upregulated circRRM2 functions an oncogenic role in BC metastasis. The positive feedback loop of circRRM2/IGF2BP1/MYC enforces the circRRM2 expression, which might offer a potential target for BC treatment.

Nucleosome sliding mechanism based on the potential energy of sequence.

Nucleosome sliding and nucleosome digestion are two main ways for regulating gene transcription. We constructed three characteristic parameters (CP) based on the information of CG0, CG1 and CG2 motifs, and used these parameters to analyze the sliding trend of -1 and +1 nucleosomes around TSS of genes with NFR in yeast. The CP distribution was used to describe the features of nucleosome sequences, and the slope of fit line of CP distribution curve was used to represent the potential energy of nucleosome sequences. Results show that nucleosome sliding trend could be reflected by CG0 and CG2 CP distributions, and CG0 CP distribution has a good correlation with nucleosome sliding trend. In addition, the sliding trend of nucleosomes is different in various expression level genes. For high expression gene, sliding trend of -1 nucleosome is weaker and that of +1 nucleosome is stronger.

Transcriptome profile analysis reveals a silica-induced immune response and fibrosis in a silicosis rat model.

Silicosis is a type of pneumoconiosis caused by the inhalation of silica dust. It is characterized by inflammation and fibrosis of the lung. Although many studies have reported that crystalline silica-inhalation into the lung initiates the immune response, activating effector cells and triggering the inflammatory cascade with subsequent elaboration of the extracellular matrix and fibrosis, the mechanism of silicosis pathogenesis remains unclear. In the present study, we established a silica inhalation-induced silicosis rat model validated by histological and cytokine analyses. RNA-seq and bioinformatic analyses showed that 600 genes were upregulated and 537 genes were downregulated in the silica-treated group. GO enrichment analysis indicates that these differentially expressed genes are enriched in several biological processes including immune response and organism remodeling. KEGG enrichment analysis showed that 53 enriched pathways were mainly associated with human diseases, immune response, signal transduction, and fibrosis process. Since alternative splicing of pre-mRNAs is also essential for the regulation of gene expression, we identified several alternative pre-mRNA splicing events in the fibrotic process. This study will provide a foundation to understand the molecular mechanism of the pulmonary fibrosis caused by silica.