Kate Hua | National Yang Ming Chiao Tung University (original) (raw)

Papers by Kate Hua

Journal of Ethnopharmacology

Nature Communications

Regulation of fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (... more Regulation of fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (LDs), is closely related to lipid homeostasis, adipocyte hypertrophy and obesity. We report here that stomatin, a major constituent of lipid raft, participates in adipogenesis and adipocyte maturation by modulating related signaling pathways. In adipocyte-like cells, increased stomatin promotes LD growth or enlargements by facilitating LD-LD fusion. It also promotes fatty acid uptake from extracellular environment by recruiting effector molecules, such as FAT/CD36 translocase, to lipid rafts to promote internalization of fatty acids. Stomatin transgenic mice fed with high-fat diet exhibit obesity, insulin resistance and hepatic impairments; however, such phenotypes are not seen in transgenic animals fed with regular diet. Inhibitions of stomatin by gene knockdown or OB-1 inhibit adipogenic differentiation and LD growth through downregulation of PPARγ pathway. Effects of stomatin on PPARγ...

International Journal of Medical Sciences

Purpose: The alteration of the exosomal proteins in the aqueous humor (AH) is linked to the devel... more Purpose: The alteration of the exosomal proteins in the aqueous humor (AH) is linked to the development of eye diseases. The goal of this study was to examine the exosomal protein profile of patients with age-related macular degeneration (AMD) to better understand their role in the pathogenesis of AMD. Methods: Exosomes were isolated from the AH of 28 AMD and 25 control eyes. The quality, concentration, and size distribution of exosomes were measured using a nanoparticle tracking analysis system (NTA). Total exosomal proteins from each sample were purified and digested with trypsin for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: Based on LC-MS/MS analysis, we got 105 exosomal peptides from AMD and control patients. Gene ontology (GO) analysis in the biology process revealed that exosomal proteins of AMD were enriched in the lipoprotein metabolic process. T-test analysis revealed six exosomal proteins in patients with AMD were significantly different from controls. Comparing the exosomal protein profile of AMD patients who were receiving anti-VEGF therapy, we observed the amount of two proteins decreased with the duration of the anti-VEGF treatment time. Conclusions: In this study, we successfully isolated and purified AH exosomes. Our results provide pioneering findings for the exosomal protein profile in AMD development and under therapy. These unique proteins could be the new targets for drug discovery or biological markers for evaluating therapeutic efficacy.

International Journal of Medical Sciences, 2021

Objectives: Myopia is the most common refractive vision disorder. In recent years, several studie... more Objectives: Myopia is the most common refractive vision disorder. In recent years, several studies have suggested that the alteration of the exosomal protein levels in the aqueous humor (AH) is associated with the development of several eye diseases. Therefore, we aimed to explore the exosomal protein profile of the AH from myopia patients. Methods: Exosomes were isolated from the AH. The quality, concentration, and size distribution of exosomes for each patient were measured using nanoparticle tracking analysis system. Then, the exosomal proteins were purified and digested by trypsin for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: There was no significant difference observed between the myopia and control when comparing the concentration and size distribution of exosomes in the AH for each sample. Based on LC-MS/MS analysis, myopia patients had higher and more complex exosomal peptide content. We found two proteins that were common in AH exosomes and eight proteins that were highly expressed in the myopia group. Conclusions: Our results provide pioneering findings for the exploration of the exosomal protein profile in myopia development. Further studies may provide significant information for the diagnosis, clinical treatment, and prognosis of myopia.

Table S1. The expression fold changes of cardiac function-associated genes during aging process. ... more Table S1. The expression fold changes of cardiac function-associated genes during aging process. Table S2. The expression fold changes of genes relating to metabolism during aging process. Table S3. The expression fold changes of immune-related genes during aging process. Table S4. The expression fold changes of genes relating to vessel functions during aging process. (DOCX 37 kb)

Oncology letters, 2018

Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor sup... more Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor suppressors or oncogenes in human cancer. The present study identified the miR-23a/27a/24-2 cluster, containing miR-23, miR-27a and miR-24, as an oncogene in gastric cancer. The expression of the miR-23a/27a/24-2 cluster was upregulated in clinical gastric cancer tissues. Transfection with inhibitors of miR-23a, miR-27a, or miR-24, either independently or together, repressed colony formation and tumor formation. The miR23a/27a/24-2 cluster inhibitors repressed the growth of gastric cancer cells in a synergistic manner. In addition, treatment with lower doses of the miRNA inhibitor mixture induced the formation of apoptotic bodies. According to computational predictions using TargetScan, suppressor of cytokine-induced signaling 6 (SOCS6) was identified as one of the downstream target genes of the miR-23a/27a/24-2 cluster. The expression of SOCS6 was significantly lower in tumor tissues than ...

Oncology reports, Jan 6, 2017

Gene fusion due to rearrangement or translocation of chromosomes is a powerful mutational mechani... more Gene fusion due to rearrangement or translocation of chromosomes is a powerful mutational mechanism during tumorigenesis. Several new high-resolution technologies have recently been developed to evaluate large numbers of small aberrations as candidate loci for fusion gene screening. In our previous whole-genome screening study using 500K SNP arrays, we identified more than 700 homozygous deletions (HDs) and amplicons in 23 cancer cell lines. To explore novel fusion genes in cancer, we established stringent criteria for defining HD and amplicon breakpoints. Then genomic PCR and sequencing analyses identified a fusion gene, FNDC3B-PRKCI, that resulted from chromosome intra-rearrangement. Western blotting and 3'-RACE analyses revealed that the chimeric transcript was an in-frame fusion between FNDC3B and PRKCI. Finally, cell migration and colony formation assays suggested that FNDC3B-PRKCI is a potential oncogene.

Oncology Reports, 2015

Krüppel-like factor 4 (KLF4) plays important roles in development, stemness and tumorigenesis; ho... more Krüppel-like factor 4 (KLF4) plays important roles in development, stemness and tumorigenesis; however limited information is available on the detailed function of KLF4 in hepatocellular carcinoma (HCC). The objective of the present study was to examine the functional roles of KLF4 in the metastasis of HCC cells. KLF4 was overexpressed and knocked down by lentiviral transduction method in highly metastatic HCC cells. KLF4 overexpression in HCC cells led to inhibition of cell migration and invasion. These inhibitory effects were associated with the upregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 by KLF4. Treatment with recombinant TIMP-1 decreased the migratory ability of HCC cells. Moreover, myeloperoxidase (MPO)-TIMP-1/TIMP-2 inactivator counteracted the KLF4-induced inhibition of cell migration/invasion. Consistently, KLF4 knockdown in HCC cells downregulated TIMP-1 and TIMP-2 expression, consequently promoting cell migration and invasion. Furthermore, we found that KLF4 regulated E-cadherin and epithelialmesenchymal transition (EMT)-related proteins such as snail, vimentin and Bmi1 to modulate the cell migration ability. These results together demonstrated for the first time that KLF4 plays an important role in inhibiting the aggressiveness of HCC cells via upregulation of TIMP-1 and TIMP-2.

Cancers, 2011

We have previously identified large megabase-sized hypomethylated zones in the genome of the brea... more We have previously identified large megabase-sized hypomethylated zones in the genome of the breast cancer cell line MCF-7 using the TspRI-ExoIII technique. In this report, we used a more convenient high throughput method for mapping the hypomethylated zones in a number of human tumor genomes simultaneously. The method was validated by the bisulfite sequencing of 39 randomly chosen sites in a demethylated domain and by bisulfite genome-wide sequencing of the MCF-7 genome. This showed that the genomes of the various tumor cell lines, as well as some primary tumors, exhibit common hypomethylated domains. Interestingly, these hypomethylated domains are correlated with low CpG density distribution genome-wide, together with the histone H3K27Me3 landscape. Furthermore, they are inversely correlated with the H3K9Ac landscape and gene expression as measured in MCF-7 cells. Treatment with drugs resulted in en-bloc changes to the methylation domains. A close examination of the methylation

BMC Genetics, 2018

Background: Aging leads to decreased skeletal muscle function in mammals and is associated with a... more Background: Aging leads to decreased skeletal muscle function in mammals and is associated with a progressive loss of muscle mass, quality and strength. Age-related muscle loss (sarcopenia) is an important health problem associated with the aged population. Results: We investigated the alteration of genome-wide transcription in mouse skeletal muscle tissue (rectus femoris muscle) during aging using a high-throughput sequencing technique. Analysis revealed significant transcriptional changes between skeletal muscles of mice at 3 (young group) and 24 (old group) months of age. Specifically, genes associated with energy metabolism, cell proliferation, muscle myosin isoforms, as well as immune functions were found to be altered. We observed several interesting gene expression changes in the elderly, many of which have not been reported before. Conclusions: Those data expand our understanding of the various compensatory mechanisms that can occur with age, and further will assist in the development of methods to prevent and attenuate adverse outcomes of aging.

The Tohoku Journal of Experimental Medicine

Myopia is the most common refractive disorder in Eastern Asia. The development of myopia is assoc... more Myopia is the most common refractive disorder in Eastern Asia. The development of myopia is associated with the cooperation of various ocular tissues. Exosomes in the aqueous humor (AH) have been implicated to modulate intracellular communications by transferring exosomal miRNAs and proteins between cells. These exosomal miRNAs and proteins are likely involved in the pathogenesis of various eye diseases. In this study, we aimed to explore human exosomal miRNA profiles and their roles in myopia development. AH samples were collected from 16 patients (8 myopia and 8 control) undergoing routine cataract surgeries. Exosomes were isolated from AH of each individual using the ExoQuick solution. The numbers and sizes of exosomes were not significantly different between the myopia and control groups. The individual exosomes of the same group were pooled to purify RNA. Unexpectedly, the myopia group contained 2.78-fold total RNA amount than that in the control group. Thereafter, miRNA profiles were analyzed using the OpenArray system. We thus found 15 myopia-specific miRNAs and four myopia-absent miRNAs. By using bioinformatics analysis, we identified six well-known myopia-associated genes that are potential targets of five myopia-specific miRNAs (has-miR-582-3p, has-miR-17-5p, has-miR-885-3p, has-miR-19b-3p, and has-miR-450b-5p). These genes are cholinergic receptor muscarinic 2 (CHRM2), cyclic nucleotide-gated channel beta 3 (CNGB3), vascular endothelial growth factor A (VEGFA), adenosine A2a receptor (ADORA2A), insulin-like growth factor 1 (IGF1), and lumican (LUM). Moreover, CHRM2 may be a target of myopia-absent miRNA (has-miR-378a-5p). In conclusion, we show the expression profiles of AH-derived exosomal miRNAs and their potential roles in myopia development.