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Biomedical subjects

Da Yang

Publications and source records attributed to Da Yang.

4 recordsLinked to original sources

MYC-bound enhancer RNAs in cis regulate gene transcription and tumorigenesis.

Emerging evidence suggests that MYC binds RNAs, but its functional consequences remain unclear. Here, we integrate multiomics data and reveal that MYC broadly binds enhancer RNAs (eRNAs), which exhibit high cancer- and tissue-specific expression in cancer cell lines and patient tumors. Moreover, we developed a computational pipeline to identify potential cis-regulatory MYC-eRNA target genes, with most predicted eRNA-target pairs supported by RNA polymerase II-mediated chromatin interaction data. Among these, we functionally characterized MERG1 as an oncogenic eRNA that promotes breast cancer tumorigenesis. Mechanistically, MERG1 interacts with MYC to enhance its occupancy at the GREB1 promoter, driving chromatin remodeling and epigenetic activation. This process specifically amplifies GREB1 expression and promotes tumor progression. Last, nanoparticle-mediated delivery of antisense oligonucleotides targeting MERG1 suppresses MYC-mediated breast cancer growth. These results advance our understanding of the enhancer-driven regulation of gene expression and tumorigenesis and provide insights into the regulatory landscape of MYC in cancer.

Humans↗

Effects of replacing the unreliable cDNA microarray measurements on the disease classification based on gene expression profiles and functional modules.

MOTIVATION: Microarrays datasets frequently contain a large number of missing values (MVs), which need to be estimated and replaced for subsequent data mining. The focus of the paper is to study the effects of different MV treatments for cDNA microarray data on disease classification analysis. RESULTS: By analyzing five datasets, we demonstrate that among three kinds of classifiers evaluated in this study, support vector machine (SVM) classifiers are robust to varied MV imputation methods [e.g. replacing MVs by zero, K nearest-neighbor (KNN) imputation algorithm, local least square imputation and Bayesian principal component analysis], while the classification and regression tree classifiers are sensitive in terms of classification accuracy. The KNNclassifiers built on differentially expressed genes (DEGs) are robust to the varied MV treatments, but the performances of the KNN classifiers based on all measured genes can be significantly deteriorated when imputing MVs for genes with larger missing rate (MR) (e.g. MR > 5%). Generally, while replacing MVs by zero performs relatively poor, the other imputation algorithms have little difference in affecting classification performances of the SVM or KNN classifiers. We further demonstrate the power and feasibility of our recently proposed functional expression profile (FEP) approach as means to handle microarray data with MVs. The FEPs, which are derived from the functional modules that are enriched with sets of DEGs and thus can be consistently identified under varied MV treatments, achieve precise disease classification with better biological interpretation. We conclude that the choice of MV treatments should be determined in context of the later approaches used for disease classification. The suggested exclusion criterion of ignoring the genes with larger MR (e.g. >5%), while justifiable for some classifiers such as KNN classifiers, might not be considered as a general rule for all classifiers.

Algorithms↗

Cubic liquid-crystalline nanoparticles.

Cubic liquid-crystalline nanoparticles prepared from aqueous dispersions of cubic lipid-water phases are kinetically stable in the presence of certain dispersing agents. The properties of cubic nanoparticles from monoolein-water and other lipid-water systems have been examined with a variety of experimental techniques. The cubic nanoparticles can be stabilized by polymerization of the reactive lipids in cubic lipid assemblies. Several low-energy-input methods have been developed to facilitate the production and application of cubic nanoparticles. The ability to incorporate and deliver lipophilic, amphiphilic, and water-soluble molecules in a controlled manner and the good biocompatibility of cubic nanoparticles make them excellent candidates for drug-delivery applications.

Journal Article↗

Polymerized bicontinuous cubic nanoparticles (cubosomes) from a reactive monoacylglycerol.

Bicontinuous cubic phases of monoacylglycerides/Poloxamer 407 (PEO98PPO67PEO98)/water can be dispersed into submicron particles, which are termed "cubosomes". Technological applications of these nanoparticles may be possible, if their nonlamellar architecture can be rendered more robust. To accomplish this goal, a polymerizable heterobifunctional monoacylglycerol, 3-(2,4,13-(E,E)-tetradecatrienoyl)-sn-glycerol (1), was synthesized and combined with water to form an optically transparent gel. In the presence of Poloxamer 407 and excess water the cubic phase of 1 was dispersed by ultrasonication into 300-nm diameter nanoparticles. The polymerization of these reactive cubosomes could be initiated either by the use of a photoinitiator or with redox chemistry. The polymerized cubosomes remained stable even after the addition of excess Triton X-100, in a manner consistent with executing cross-linking in the nanostructures.

Cross-Linking Reagents↗