Hsuan-Cheng Huang

National Yang Ming University | NYMU · Institute of Biomedical Informatics

Background Recently, non-coding RNAs are of growing interest, and more scientists attach importance to research on their functions. Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts longer than 200 nucleotides. We already knew that lncRNAs are related to cancers and will be dysregulated in them. But most of their function...

Post-COVID-19 pulmonary fibrosis (PCPF) is a long-term complication that appears in some COVID-19 survivors. However, there are currently limited options for treating PCPF patients. To address this problem, we investigated COVID-19 patients’ transcriptome at single-cell resolution and combined biological network analyses to repurpose the drugs trea...

The tumor microenvironment (TME), which comprises cellular and noncellular components, is involved in the complex process of cancer development. Emerging evidence suggests that mesenchymal stem cells (MSCs), one of the vital regulators of the TME, foster tumor progression through paracrine secretion. However, the comprehensive phospho-signaling pat...

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necess...

Single-cell RNA sequencing (scRNA-seq) approach can broadly and specifically evaluate the individual cells with minimum detection bias. To explore the individual compositional and transcriptional alteration of intestinal leukocytes in the Dual Specificity Phosphatase 6 knockout (D6KO) mice, we performed a scRNA-seq followed by the cell type annotat...

DNA replication is initiated with the recognition of the starting point of multiple replication forks by the origin recognition complex and activation of the minichromosome maintenance complex 10 (MCM10). Subsequently, DNA helicase, consisting of the MCM protein subunits MCM2-7, unwinds double-stranded DNA and DNA synthesis begins. In previous stud...

Background Increasing amount of long non-coding RNAs (lncRNAs) have been found involving in many biological processes and played salient roles in cancers. However, up until recently, functions of most lncRNAs in lung cancer have not been fully discovered, particularly in the co-regulated lncRNAs. Thus, this study aims to investigate roles of lncRNA...

Tissue-resident macrophages are essential for protection from pathogen invasion and maintenance of organ homeostasis. The ability of thymic macrophages to engulf apoptotic thymocytes is well appreciated, but little is known about their ontogeny, maintenance, and diversity. Here, we characterized the surface phenotype and transcriptional profile of...

Background A new class of regulatory elements called super-enhancers, comprised of multiple neighboring enhancers, have recently been reported to be the key transcriptional drivers of cellular, developmental, and disease states. Results Here, we defined super-enhancer RNAs as highly expressed enhancer RNAs that are transcribed from a cluster of lo...

Mitochondria are crucial organelles that provide energy via oxidative phosphorylation in eukaryotic cells and also have critical roles in growth, division, and the cell cycle, as well as the rapid adaptation required to meet the metabolic needs of the cell. Mitochondrial processes are highly dynamic; fusion and fission can vary with cell type, cell...

Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the e...

Motivation The hourglass model is a popular evo-devo model depicting that the developmental constraints in the middle of a developmental process are higher, and hence the phenotypes are evolutionarily more conserved, than those that occur in early and late ontogeny stages. Although this model has been supported by studies analyzing developmental ge...

Despite the fact that an increased amount of survival-related lncRNAs have been found in cancer, few drugs that target lncRNAs are approved for treatment. Here, we developed a network-based algorithm, LncTx, to repurpose the medications that potentially act on survival-related lncRNAs in lung cancer. We used eight survival-related lncRNAs derived f...

Metformin is one of the most widely used anti-diabetic drugs in type-II diabetes treatment. The mechanism of decreasing blood glucose is believed to suppress hepatic gluconeogenesis by increasing muscular glucose uptake and insulin sensitivity. Recent studies suggest that metformin may reduce cancer risk; however, its anticancer mechanism in gastri...

Background: ZNF322A is an oncogenic transcription factor that belongs to the Cys2His2-type zinc-finger protein family. Accumulating evidence suggests that ZNF322A may contribute to the tumorigenesis of lung cancer, however, the ZNF322A-mediated downstream signaling pathways remain unknown. Methods: To uncover ZNF322A-mediated functional network,...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent for the outbreak of coronavirus disease 2019 (COVID-19). This global pandemic is now calling for efforts to develop more effective COVID-19 therapies. Here we use a host-directed approach, which focuses on cellular responses to diverse small-molecule treatments, to id...

Ectopic adenosine triphosphate (eATP) synthase, located on the cell surface instead of the mitochondrial inner membrane, has been discovered to be a novel target for the treatment of various types of cancer. However, the mechanism of eATP synthase trafficking toward the cell surface remains unclear. In this study, we used an integrative approach in...

The current state of the COVID-19 pandemic is a global health crisis. To fight the novel coronavirus, one of the best-known ways is to block enzymes essential for virus replication. Currently, we know that the SARS-CoV-2 virus encodes about 29 proteins such as spike protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), Papain-lik...

The EGFR tyrosine kinase inhibitor gefitinib is commonly used for lung cancer patients. However, some patients eventually become resistant to gefitinib and develop progressive disease. Here, we indicate that ecto-ATP synthase, which ectopically translocated from mitochondrial inner membrane to plasma membrane, is considered as a potential therapeut...

Background: Leaky gut and microbiota dysbiosis have been linked to many chronic inflammatory diseases. Strengthening the gut epithelial barrier is a novel but overlooked strategy for management of gut microbiota-associated illnesses. Results: Using the dextran sulfate sodium (DSS)-induced gut barrier injury-based colitis model, we found that DSS-in...

Lung cancer is a leading cause of death. Most previous studies have been based on traditional cell-culturing methods. However, lung cells are periodically subjected to mechanical forces during breathing. Understanding the mechanisms underlying the cyclic stretching induced in lung cells may be important for lung cancer therapy. Here, we applied cyc...

Gastric cancer is one of the most common types of cancer worldwide. Nevertheless, effective therapeutic strategies have not yet been discovered. Several studies have shown that tanshinone IIA (TIIA), which is extracted from the traditional herbal medicine plant Danshen (Salvia miltiorrhiza), has potential activity against many kinds of cancer. Our...

Most hepatocellular carcinomas (HCCs) develop in patients with chronic hepatitis, which creates a microenvironment for the growth of hepatic progenitor cells (HPCs) at the periportal area and subsequent development of HCCs. We investigated the signal from the inflammatory liver for this pathogenic process in the hepatic conditional β-catenin knocko...

Background: Super-enhancer RNAs (seRNAs) are a kind of noncoding RNA transcribed from super-enhancer regions. The regulation mechanism and functional role of seRNAs are still unclear. Although super-enhancers play a critical role in the core transcriptional regulatory circuity of embryonic stem cell (ESC) differentiation, whether seRNAs have simil...

MYCN-amplified (MNA) neuroblastoma is an aggressive neural crest-derived pediatric cancer. However, MYCN is indispensable for development and transcriptionally regulates extensive network of genes. Integrating anti-MYCN ChIP-seq and gene expression profiles of neuroblastoma patients revealed the metabolic enzymes, MTHFD2 and PAICS, required for one...

The microbiome is recognized as a quasi-organ in the human body. When dysbiosis of the microbiome occurs, this variation may contribute to alterations in the microenvironment, potentially inducing an inflammatory immune response and providing a niche for neoplastic growth. However, there is limited evidence regarding the correlation and interaction...

The microbiome is recognized as a quasi-organ in the human body. In particular, the gut microbiome is correlated with immune function, metabolism, and tumorigenesis. When dysbiosis of the microbiome occurs, this variation may contribute to alterations in the microenvironment, potentially inducing an inflammatory immune response and providing a nich...

Neuroblastoma is a neural crest-derived embryonal tumor and accounts for about 15% of all cancer deaths in children. MYCN amplification is associated with aggressive and advanced stage of high-risk neuroblastoma which remains difficult to treat and exhibit poor survival under current multimodality treatment. Here, we analyzed the transcriptomic pro...

Table S9. Expression-Based Single Therapeutics across Cancer Types, Related to Figure 7

Table S11. Comparison with Metastatic GEP-NET Master-Regulator-Targeting Compounds Identified by OncoTreat, Related to Figure 7

Table S3. Mapping of Compounds and Genes between DrugBank and LINCS, Related to Figure 3

Table S6. Overlapping Compound-Transcript and Sensitivity-Expression Pairs, Related to Figure 6

Table S10. Predicted Synergistic Drug Combinations across Cancer Types, Related to Figure 7

Table S2. Recurrent Perturbation-Transcript Regulatory Relationships, Related to Figure 2

Table S7. Overlapping MoA-Transcript and Sensitivity-Expression Pairs, Related to Figure 6

Table S8. Differentially Expressed Genes across Eight TCGA Cancer Types, Related to Figure 7

Cancer is a complex disease that relies on both oncogenic mutations and non-mutated genes for survival, and therefore coined as oncogene and non-oncogene addictions. The need for more effective combination therapies to overcome drug resistance in oncology has been increasingly recognized, but the identification of potentially synergistic drugs at s...

Purpose: Neuroblastoma is a pediatric malignancy of the sympathetic nervous system with diverse clinical behaviors. Genomic amplification of MYCN oncogene has been shown to drive neuroblastoma pathogenesis and correlate with aggressive disease, but the survival rates for those high-risk tumors carrying no MYCN amplification remain equally dismal. T...

The interaction of long noncoding RNAs (lncRNAs) with one or more RNA-binding proteins (RBPs) are important to a plethora of cellular and physiological processes. The lncRNA SNHG1 was reported to be aberrantly expressed and associated with poor patient prognosis in several cancers, including neuroblastoma. However, the interacting RBPs and biologic...

Background: Current clinical risk factors stratify patients with neuroblastoma (NB) for appropriate treatments, yet patients with similar clinical behaviors evoke variable responses. MYCN amplification is one of the established drivers of NB and, when combined with high-risk displays, worsens outcomes. Growing high-throughput transcriptomics studi...

Alternative polyadenylation (APA) affects the length of the 3' untranslated region (3'-UTR) and the regulation of microRNAs. Previous studies have shown that cancer cells tend to have shorter 3'-UTRs than normal cells. A plausible explanation for this is that it enables cancer cells to escape the regulation of microRNAs. Here, we extend this concep...

Table S3. Number of Analyzed LINCS Perturbagens across 10 Cell Types, Related to Figure 3

Table S7. d6 RSS Network Communities and their Enrichment Analyses, Related to Figure 4

Table S8. d24 RSS Network Communities and their Enrichment Analyses, Related to Figure 4

Table S1. Selected Drugs for Parameter Optimization in Intensity-Based Clustering, Related to Figure 2

Table S9. sh96 RSS Network Communities and their Enrichment Analyses, Related to Figure 4

Biological systems often respond to a specific environmental or genetic perturbation without pervasive gene expression changes. Such robustness to perturbations, however, is not reflected on the current computational strategies that utilize gene expression similarity metrics for drug discovery and repositioning. Here we propose a new expression-int...

A new class of regulatory elements called super-enhancers, comprised of multiple neighboring enhancers, have recently been reported to be the key transcriptional drivers of cellular, developmental, and disease states. Here, we propose to define super-enhancer RNA as highly expressed enhancer RNAs that are transcribed from a cluster of localized gen...

DNA replication control is vital for maintaining genome stability and the cell cycle, perhaps most notably during cell division. Malignancies often exhibit defective minichromosome maintenance protein 2 (MCM2), a cancer proliferation biomarker that serves as a licensing factor in the initiation of DNA replication. MCM2 is also known to be one of th...