Ku-Chung Ku-Chung ChenTaipei Medical University | TMU · Department of Biochemistry
Ku-Chung Ku-Chung Chen
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86
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Introduction
Publications
Publications (86)
Nontyphoidal Salmonella (NTS) is a major foodborne pathogen causing from acute gastroenteritis to bacteremia, particularly in pediatric and elderly patients. Antimicrobial resistance of NTS, especially resistance to extended-spectrum cephalosporins, has emerged over the past decades. Thirteen NTS isolates resistant to ceftriaxone or cefotaxime were...
Purpose:
We previously reported miR-328-3p as a novel risk factor for myopia through a genetic association study of the PAX6 gene. In the present study, we first explored the effects of miR-328-3p on other myopia-related genes, and then tested whether anti-miR-328-3p may be used for myopia control.
Methods:
The luciferase report assay and transi...
The insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β signal pathways are both recognized as important in regulating cancer prognosis, such as the epithelial-to-mesenchymal transition (EMT) and cell invasion. However, cross-talk between these two signal pathways in glioblastoma multiforme (GBM) is still unclear. In the prese...
An insufficient oxygen supply within the intratumoral environment, also known as hypoxia, induces glioblastoma multiforme (GBM) invasion, stemness, and temozolomide (TMZ) drug resistance. Long non-coding (lnc)RNAs have been reported to involve in hypoxia and GBM progression. However, their roles in hypoxic GBM malignancy are still unclear. We inves...
Background: Heterogeneous features of lung adenocarcinoma (LUAD) are used to stratify patients into terminal respiratory unit (TRU), proximal-proliferative (PP), and proximal-inflammatory (PI) subtypes. A more-accurate subtype classification would be helpful for future personalized medicine. However, these stratifications are based on genes with va...
Aims
Immune checkpoints regulate immunity to prevent autoimmunity and protect the host from damage during pathogenic infection. They also participate in subverting immune surveillance and promote antitumor immunity in cancers. Although immunotherapy improves clinical outcomes, not all cancer patients experience expected responses after therapy. Hen...
Background
Long noncoding (lnc)RNAs and glycolysis are both recognized as key regulators of cancers. Some lncRNAs are also reportedly involved in regulating glycolysis metabolism. However, glycolysis-associated lncRNA signatures and their clinical relevance in cancers remain unclear. We investigated the roles of glycolysis-associated lncRNAs in can...
Limited therapeutic efficacy of temozolomide (TMZ) against glioblastomas highlights the importance of exploring new drugs for clinical therapy. Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, is currently being tested as therapy for glioblastomas. Unfortunately, sunitinib still has insufficient activity to cure glioblastomas. Our aim...
Aims
Xanthohumol (XN), a natural prenylated flavonoid isolated from Humulus lupulus L. (hops), possess the therapeutic effects in glioblastoma multiforme (GBM), which is a grade IV aggressive glioma in adults. However, low bioavailability and extractive yield limit the clinical applications of XN. To comprehensively investigate XN-mediated gene net...
DNA damage-inducible transcript 4 (DDIT4) is known to participate in various cancers, including glioblastoma multiforme (GBM). However, contradictory roles of DDIT4 exist in inducing cell death and possessing anti-apoptotic functions against cancer progression. Herein, we investigated DDIT4 signaling in GBM and temozolomide (TMZ) drug resistance. W...
Temozolomide (TMZ) is a first-line alkylating agent for glioblastoma multiforme (GBM). Clarifying the mechanisms inducing TMZ insensitivity may be helpful in improving its therapeutic effectiveness against GBM. Insulin-like growth factor (IGF)-1 signaling and micro (mi)RNAs are relevant in mediating GBM progression. However, their roles in desensit...
Temozolomide (TMZ) is a first-line chemotherapeutic agent used against glioblastoma multiforme (GBM), but this disease exhibits recurrence and high lethality. Therefore, it is critical to explore biomarkers which involve in drug resistance and can be represented as different therapeutic effects after a diagnosis. We attempted to investigate the und...
The phthalate plasticizer, di(2‐ethyl‐hexyl) phthalate (DEHP), and its derived metabolites are common anthropogenic environmental toxins, which are known to act as endocrine disruptors. Numerous studies have associated DEHP with disruption of sex hormones, abnormal development of reproductive organs, allergies, and inflammation. Its role in promoti...
Because of innumerable cancer sequencing projects, abundant transcriptome expression profiles together with survival data are available from the same patients. Although some expression signatures for prognosis or pathologic staging have been identified from these data, systematically discovering such kind of expression signatures remains a challeng...
Tumor-infiltrating lymphocytes are related to positive clinical prognoses in numerous cancer types. Programmed death ligand 1 (PD-L1), a mediator of the PD-1 receptor, plays an inhibitory role in cancer immune responses. PD-L1 upregulation can impede infiltrating T-cell functions in lung adenocarcinoma (LUAD), a lung cancer subtype. However, associ...
Imatinib (IM) is a first-line therapeutic drug for chronic myeloid leukemia (CML), a hematological disease. Mutations in the BCR-ABL domain increase formation of IM resistance in CML. However, not all patients are BCR-ABL domain-mutant dependent. Investigating non-mutant mechanisms in the development of acquired IM resistance is a critical issue. W...
Flavonoids luteolin and quercetin can inhibit growth and metastasis of cancer cells. In our previous report, luteolin and quercetin was shown to block Akt/mTOR/c-Myc signaling. Here, we found luteolin and quercetin reduced protein level and transactivation activity of RPS19 in A431-III cells, which is isolated from parental A431 (A431-P) cell line....
The tumor microenvironment plays an important role in tumor initiation and progression. It is well documented that nicotine participates in cigarette smoking-related malignancies. Previous studies focused on the effects of nicotine on tumor cells; however, the role of the microenvironment in nicotine-mediated tumorigenesis is poorly understood. Her...
The insulin-like growth factor (IGF)-1 signaling is relevant in regulating cell growth and cytokine secretions by glioblastomas. MicroRNAs determine the cell fate in glioblastomas. However, relationships between IGF-1 signaling and miRNAs in glioblastoma pathogenesis are still unclear. Our aim was to validate the IGF-1-mediated mRNA/miRNA regulator...
Colon cancer is the third most common cancer in the world and the second most common cause of cancer-related mortality. Molecular biomarkers for colon cancer have undergone vigorous discovery and validation. Recent studies reported that overexpression of podocalyxin-like protein 1 (PODXL) is associated with distant metastasis and poor prognosis acr...
Mutation of KRAS in non-small cell lung cancer (NSCLC) shows a poor response to epidermal growth factor receptor (EGFR) inhibitors and chemotherapy. Currently, there are no direct anti-KRAS therapies available. Thus, new strategies have emerged for targeting KRAS downstream signaling. Panobinostat is a clinically available histone deacetylase inhib...
Platelet-derived growth factor (PDGF) can promote vascular smooth muscle cells (VSMCs) to switch from the quiescent contractile phenotype to synthetic phenotype, which contributes to atherosclerosis. We aimed to investigate the role of microRNA let-7g in phenotypic switching. Bioinformatics prediction was used to find let-7g target genes in the PDG...
MicroRNAs are small noncoding RNAs that post-transcriptionally control the expression of genes involved in glioblastoma multiforme (GBM) development. Although miR-302b functions as a tumor suppressor, its role in GBM is still unclear. Therefore, this study comprehensively explored the roles of miR-302b-mediated gene networks in GBM cell death. We f...
The 34 non-direct targets of miR-302b-downregulated genes.
(PDF)
Another seven target genes of miR-302b possessed characteristics similar to those of NFIA.
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Gene list from microarray analyses.
(XLSX)
Molecular and cellular functions of miR-302b-influenced genes by ingenuity pathway analysis.
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Validation of the effects of NFIA on patient survival in another GEO dataset profiling.
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Another 33 nondirect target genes of miR-302b possessed characteristics similar to those of NFIA.
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We previously reported that the dietary flavonoids, luteolin and quercetin, might inhibit the invasiveness of cervical cancer by reversing epithelial-mesenchymal transition (EMT) signaling. However, the regulatory mechanism exerted by luteolin and quercetin is still unclear. This study analyzed the invasiveness activation by ubiquitin E2S ligase (U...
[This corrects the article DOI: 10.1371/journal.pone.0156260.].
Antroquinonol (ANQ) is a ubiquinone derivative from the unique mushroom Antrodia camphorata, which exhibits broad-spectrum bioactivities. The effects of ANQ on cancer stem cell-like properties in colon cancer, however, remain unclear. In this study, we found that ANQ inhibited growth of colon cancer cells. The 50% growth inhibitions (GI50) of ANQ o...
Glioblastoma multiforme (GBM) is the high-grade primary glioma in adults. Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug for clinical therapy. However, the expense of TMZ therapy and increasing drug resistance to TMZ decreases its therapeutic effects. Therefore, our aim was to investiga...
Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagen...
Identification that PDK1 is not a direct target gene of miR-128.
(A) Schematic diagram of potential miR-128-targeted sites in the PDK1 3’-untranslated region (UTR). (B) Effects of miR-128 on PDK1 3’-UTR luciferase activity. To test for miR-128's effect, different doses of miR-128 plasmids were co-transfected with 500 ng of the pmiRGlo-PDK1 3’-UTR....
Effects of 3-MA on cell viability and autophagy formation.
(A) The cytotoxicity of 3-MA against U87-MG cell viability. After cells were treated with indicated doses of 3-MA for 24 h, cell viability was measured by an MTT assay. (B) 3-MA reduced miR-128-enhanced autophagy generation. After transfection with 750 ng of miR-128-overexpressing plasmids...
Cytotoxicity effects of temozolomide (TMZ) on U87-MG cell viability.
After cells were treated with indicated doses of TMZ for 24 h, cell viability was measured with an MTT assay. Data are the mean ± SD of three experiments. * p < 0.05.
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Array data of TMZ-mediated microRNA expressions.
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Prediction of top 10 miR-128-regulated signaling pathways.
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Comparison of endogenous levels and promoter activity between miR-128-1 and miR-128-2.
(A) Endogenous expression levels of primary miR-128-1 and miR-128-2. Relative expression levels were measured using a real-time PCR. (B) Relative promoter activities of the miR-128-1 and miR-128-2 genes. After cells were respectively transfected with 500 ng pGL3-...
Effects of shRNA and miR-128-overexpressing plasmids on indicated gene expressions and endogenous miR-128 levels.
(A) The knock-down effects on JNK1, JNK2, JNK3, c-Jun, and ATF2 gene expressions by shRNA transfection. After cells were respectively transfected with 1 μg shRNA for 24 h, cells were collected to measure protein expressions with an immu...
Prediction of the putative activator protein (AP)-1-binding site on the miR-128-1 promoter in the -1970 to -2050 bp region.
(A) Schematic diagram shows the putative AP-1-binding sequence. (B) The putative AP-1-binding site (red color) was predicted by the JASPAR database.
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Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated wheth...
Chronic myeloid leukemia (CML) is a myeloproliferative disease. Imatinib (IM), the first line treatment for CML, is excessively expensive and induces various side effects in CML patients. Therefore, it is essential to investigate a new strategy for improving CML therapy. Our immunoblot data revealed that RanGTPase activating protein 1 (RanGAP1) pro...
RanGAP1 protein was expressed in CML cells.
The RanGAP1 protein levels were measured using an immunoblot assay in granulocytes and monocytes from CML patient, and K562 cells. GAPDH was used as an internal control. The CRKL phosphorylation level on Tyr-207 is activated by BCR-ABL, which is used as a marker of CML cells.
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Combination of RanGAP1 knockdown by miR-1301 and IM treatment significantly induced BCR-ABL nuclear entrapment in miR-1301-transfected K562 cells.
K562 cells were transfected with pCDH (vector only) or the miR-1301 plasmid and subsequently treated with 250 nM IM for 48 h. The protein levels were observed using immunofluorescence staining through de...
RanGAP1 expression-associated miRNA level was decreased in K562 cells compared with that in normal monocytes and granulocytes.
(A) The list of twenty-four miRNAs significantly downregulated in K562 cells respectively compared to normal monocytes and granulocytes from healthy volunteers (FC ≦ 0.5; p value ≦ 0.05) according to the microarray data fro...
IM decreased K562 cells viability in a dose dependent manner.
The viability of K562 cells was measured by an MTT assay after treatment with the indicated doses of IM for 48 h. The results are presented as means + SD of three independent experiments. Data abcdef without the same letter are significantly different from each group (p < 0.05).
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Basic clinical parameters of the CML patients involved in the study.
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Basic clinical parameters of the healthy volunteers involved in the study.
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The dietary flavonoids luteolin and quercetin are reported to inhibit cancer mobility; however, the regulatory effect of luteolin and quercetin on RPS12 is still unclear. Here, we found that A431-III cells expressed a higher level of RPS12 than A431-P cells. The flavonoids luteolin and quercetin reduced RPS12 and c-Myc expressions via Akt/mTOR sign...
Investigating existing drugs for repositioning can enable overcoming bottlenecks in the drug development process. Here, we investigated the effect and molecular mechanism of the antipsychotic drug chlorpromazine (CPZ) and identified its potential for treating colorectal cancer (CRC). Human CRC cell lines harboring different p53 statuses were used t...
Hyperlipidemia, including the oxidized low-density lipoprotein (oxLDL) accumulation, is a risk and highly associated with the development of cancers and cardiovascular diseases. microRNA-210 (miR-210), a hypoxia-responsive microRNA regulated by HIF-1α, has been implicated in cancer and cardiovascular disease formation. Furthermore, Bioinformatics a...
The prognosis of glioblastoma remains poor, even treatment with surgery, radiation, or chemotherapy. Therefore, it is still important to develop a new strategy for treatment of glioblastoma. Previous reports demonstrated that rRNA is produced at abnormally high levels in tumor cells. Nuclear export of all non-coding RNAs are known to depend on RanG...
Antroquinonol (ANQ) is an ubiquinon derivative isolated from the mycelium of Antrodia camphorata. However, the effect of ANQ on breast cancer treatment is unknown. We found that ANQ significantly suppressed the migration and invasion of breast cancer MDA-MB-231 cells, and inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasiveness by...
In this study, we investigated the antitumor activity of a novel coumarin derivative, 5,7-dihydroxy-4-methyl-6-(3-methylbutanoyl)-coumarin (DMAC), on colorectal carcinoma. DMAC treatment resulted in substantial proapoptotic activity against colon cancer HCT116 and LoVo cells. Induction of apoptotic characteristics, including cellular shrinkage, chr...
Heme oxygenase (HO)-1 is an oxidative stress-response enzyme which catalyzes the degradation of heme into bilirubin, ferric ion, and carbon monoxide (CO). Induction of HO-1 was reported to have antitumor activity; the inhibitory mechanism, however, is still unclear. In the present study, we found that treatment with [Ru(CO)3Cl2]2 (RuCO), a CO-relea...
Background:
Osteoporosis and periodontitis are both considered global health issues that threaten postmenopausal women and the older population. However, the correlation between osteoporosis and periodontitis is still unclear.
Methods:
Using a nationwide Taiwanese population-based database, data from patients with osteoporosis (2003 to 2005; n =...
Glioblastomas, the most common primary gliomas, are characterized by increased invasion and difficult therapy. Major clinical medicines for treating gliomas merely extend the survival time for a number of months. Therefore, development of new agents against gliomas is important. Autophagy, a process for degrading damaged organelles and proteins, is...
Ultraviolet (UV)-induced damage plays a major role in ocular diseases, such as cataracts and retinal degeneration. UVB may also cause retinal phototoxicity and photic retinopathy. In this study, we explored the effects of UVB on the cell cycle and the role of silent mating type information regulation 2 homolog 1 (SIRT1) in the UVB-induced damage. U...
Purpose:
Fibroblast growth factor-10 (FGF10) can modulate extracellular matrix associated genes and, therefore, it could be a myopia susceptibility gene. This study used an animal model, single nucleotide polymorphisms (SNPs) association, and genetic functional assay to evaluate FGF10 gene for myopia.
Methods:
The expression levels of FGF10 gene...
Objective:
Single nucleotide polymorphisms (SNPs) located at microRNA (miRNA) binding sites (miR-SNPs) can affect the expression of genes. This study aimed to identify the miR-SNPs associated with atherosclerosis and stroke.
Methods:
Patients with ischemic stroke (n = 657) and stroke- and myocardial infarction-free volunteers (n = 1571) were enr...
MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression at the post-transcriptional level. MicroRNAs have emerged as key regulators of several physiological and pathophysiological processes in the cardiovascular system. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlyin...
Proliferation and migration of vascular smooth muscle cells (VSMCs) can cause atherosclerosis and neointimal formation. MicroRNAs have been shown to regulate cell proliferation and phenotype transformation. We discovered abundant expression of microRNA-195 in VSMCs and conducted a series of studies to identify its function in the cardiovascular sys...
Colorectal cancer (CRC) is associated with high recurrence and mortality. Because deregulation of microRNAs is associated with CRC development and recurrence, the expression levels of microRNAs can be a simple and reliable biomarker to detect postoperative early relapse, thereby helping physicians to treat high-risk patients more efficiently.
We us...
We showed previously that single nucleotide polymorphism (SNP) rs662702 in PAX6 may be located in a microRNA-328 binding site that causes susceptibility to high myopia. Our study was done to elucidate the role of PAX6 and its relationship with microRNA-328 in myopia.
A luciferase assay was used to confirm microRNA-328 binding to the PAX6 locus. Clo...
MicroRNA-29b has been reported to epigenetically regulate proatherogenic genes in response to oxLDL. Since transcription factors and epigenetic regulations are important mechanisms to regulate gene expression, we investigated whether these mechanisms are involved in oxLDL-induced microRNA-29b upregulation. First, we confirmed that microRNA-29b expr...
Estrogen receptor α (ERα) has been shown to protect against atherosclerosis. Methylation of the ERα gene can reduce ERα expression leading to a higher risk for cardiovascular disease. Recently, microRNAs have been found to regulate DNA methyltransferases (DNMTs) and thus control methylation status in several genes. We first searched for microRNAs i...