Ku-Chung Ku-Chung Chen

Ku-Chung Ku-Chung Chen
Taipei Medical University | TMU · Department of Biochemistry

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84
Publications
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Publications

Publications (84)
Article
Full-text available
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...
Article
Full-text available
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...
Article
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...
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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...
Article
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...
Article
Full-text available
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...
Article
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...
Article
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...
Article
Full-text available
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...
Article
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...
Article
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...
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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...
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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...
Article
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...
Article
Full-text available
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....
Article
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
Article
Full-text available
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...
Data
The 34 non-direct targets of miR-302b-downregulated genes. (PDF)
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Another seven target genes of miR-302b possessed characteristics similar to those of NFIA. (PDF)
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Gene list from microarray analyses. (XLSX)
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Molecular and cellular functions of miR-302b-influenced genes by ingenuity pathway analysis. (PDF)
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Validation of the effects of NFIA on patient survival in another GEO dataset profiling. (PDF)
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Another 33 nondirect target genes of miR-302b possessed characteristics similar to those of NFIA. (PDF)
Article
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...
Article
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...
Article
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...
Article
Full-text available
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...
Data
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....
Data
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...
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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. (TIFF)
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Array data of TMZ-mediated microRNA expressions. (XLSX)
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Prediction of top 10 miR-128-regulated signaling pathways. (DOCX)
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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-...
Data
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...
Data
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. (TIFF)
Article
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...
Article
Full-text available
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...
Data
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. (TIFF)
Data
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...
Data
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...
Data
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). (TIFF)
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Basic clinical parameters of the CML patients involved in the study. (TIFF)
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Basic clinical parameters of the healthy volunteers involved in the study. (TIFF)
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
Full-text available
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 =...
Article
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...
Article
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...