Annotating regulatory elements by heterogeneous network embedding.

MOTIVATION: Regulatory elements (REs), such as enhancers and promoters, are known as regulatory sequences functional in a heterogeneous regulatory network to control gene expression by recruiting transcription regulators and carrying genetic variants in a context specific way. Annotating those REs relies on costly and labor-intensive next-generation sequencing and RNA-guided editing technologies in many cellular contexts. RESULTS: We propose a systematic Gene Ontology Annotation method for Regulatory Elements (RE-GOA) by leveraging the powerful word embedding in natural language processing. We first assemble a heterogeneous network by integrating context specific regulations, protein-protein interactions and gene ontology (GO) terms. Then we perform network embedding and associate regulatory elements with GO terms by assessing their similarity in a low dimensional vector space. With three applications, we show that RE-GOA outperforms existing methods in annotating TFs' binding sites from ChIP-seq data, in functional enrichment analysis of differentially accessible peaks from ATAC-seq data, and in revealing genetic correlation among phenotypes from their GWAS summary statistics data. AVAILABILITY AND IMPLEMENTATION: The source code and the systematic RE annotation for human and mouse are available at https://github.com/AMSSwanglab/RE-GOA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non-small-cell lung cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly implicated in the regulation of the progression of malignancy. AIM: To clarify the relations among BCYRN1 (brain cytoplasmic RNA 1, a long non-coding RNA), c-MYC and cell metastasis of non-small-cell lung cancer (NSCLC). METHODS: Real-time PCR was used to measure expression of BCYRN1 in NSCLC. Knockdown and overexpression of c-MYC were respectively performed using shRNA and lentivirus to investigate its effect on BCYRN1 expression. BCYRN1 was respectively knockdown and overexpressed by siRNA and BCYRN1 mimics to investigate its role in regulating cell metastasis in vitro. ChIP (chromatin immunoprecipitation) assay was performed to confirm the binding of c-MYC to the promoter of BCYRN1. Expression levels of matrix metalloproteinases (MMP9 and MMP13) were determined using real-time PCR and Western blotting. RESULTS: BCYRN1 is upregulated and targeted by c-MYC in NSCLC, leading to the increase of cell motility and invasiveness. RNA interference and lentivirus infection showed a positive correlation between the expressions of c-MYC and BCYRN1. ChIP assay confirmed the binding of c-MYC to the promoter region of BCYRN1 gene. In-vitro cell metastasis experiments demonstrated that BCYRN1 was necessary in the c-MYC-regulated cell migration and invasion. The mRNA and protein expression levels of MMP9 and MMP13 descended with the decreasing BCYRN1 level and ascended with the upregulation of BCYRN1. CONCLUSION: These findings uncover a regulatory mechanism in NSCLC cells involving the metastasis-promoting lncRNA BCYRN1 that improves expressions of the key metastasis-supporting proteins MMP9 and MMP13.

The value of KL-6 in the diagnosis and assessment of interstitial lung disease.

OBJECTIVE: To investigate the value of Krebs von den Lungen-6 (KL-6) in the diagnosis and activity assessment of interstitial lung disease (ILD). METHODS: The data of 69 ILD patients admitted to our hospital from January 2018 to January 2020 were analyzed retrospectively, and they were included in the ILD group. In addition, 69 patients with connective tissue disease (CTD) admitted to our hospital during the same period were selected and included in the non-ILD (NILD) group. The lung function, pulmonary imaging scores, and KL-6 expression levels were compared between the two groups. The patients in the ILD group were divided into two subgroups: the inactive group and the active group. The pulmonary function, pulmonary imaging scores, and the KL-6 expression levels of the patients in the two subgroups were compared. The value of KL-6 in the diagnosis and the ILD activity evaluation were analyzed. RESULTS: The FEV1, FVC, and DLCO levels in the LID group were lower than they were in the NLID group (P<0.05). The LUS and Warrick scores in the LID group were higher than they were in the NLID group (P<0.05). The FEV1, FVC, and DLCO levels in the active group were lower than they were in the inactive group (P<0.05). The LUS and Warrick scores in the active group were higher than they were in the NLID group (P<0.05). The patients' serum KL-6 levels in the ILD group were higher than they were in the NILD group (P<0.05), and the patients' serum KL-6 levels in the ILD group were higher than they were in the inactive group (P<0.05). The Youden's index of serum KL-6 for the diagnosis of ILD was 421.775 U/ml and the sensitivity and specificity of the serum KL-6 were 91.304% and 95.652%, respectively, showing a high diagnostic value (P<0.05). The Youden's index of the serum KL-6 levels for the evaluation of the ILD activity was den Lungen-6 (KL-, with a sensitivity of 60.976% and a specificity of 100%, showing a moderate evaluation value (P<0.05). CONCLUSION: KL-6 has a high value in the diagnosis of interstitial lung disease, and a moderate value in the assessment of interstitial lung disease activity.