Chau-ting Yeh - Academia.edu (original) (raw)

Papers by Chau-ting Yeh

Cells, 2020

Long intergenic non-coding RNAs (lincRNAs) play important roles in human cancer development, incl... more Long intergenic non-coding RNAs (lincRNAs) play important roles in human cancer development, including cell differentiation, apoptosis, and tumor progression. However, their underlying mechanisms of action are largely unknown at present. In this study, we focused on a novel suppressor lincRNA that has the potential to inhibit progression of human hepatocellular carcinoma (HCC). Our experiments disclosed long intergenic non-protein coding RNA 1488 (LINC01488) as a key negative regulator of HCC. Clinically, patients with high LINC01488 expression displayed greater survival rates and better prognosis. In vitro and in vivo functional assays showed that LINC01488 overexpression leads to significant suppression of cell proliferation and metastasis in HCC. Furthermore, LINC01488 bound to cyclin E to induce its ubiquitination and reduced expression of vimentin mediated by both miR-124-3p/miR-138-5p. Our results collectively indicate that LINC01488 acts as a tumor suppressor that inhibits me...

Journal of clinical microbiology, 1996

By using an amplification-created restriction site method, the precore TAG mutant of hepatitis B ... more By using an amplification-created restriction site method, the precore TAG mutant of hepatitis B virus was detected in 6 (75%) of 8 acute fulminant hepatitis B patients, 7 (58%) of 12 acute self-limiting hepatitis B patients, 35 (81%) of 43 hepatitis B virus surface antigen carriers with fulminant hepatitis, and 42 (70%) of 60 hepatitis B virus surface antigen carriers with chronic hepatitis. The precore TAG mutant prevails in acute and chronic hepatitis B of various severity in this area where hepatitis B is endemic.

Journal of Cancer, 2019

Background: The Aldehyde dehydrogenase 2 (ALDH2) mutant genotypes contain an allele encoding defe... more Background: The Aldehyde dehydrogenase 2 (ALDH2) mutant genotypes contain an allele encoding defective ALDH2 with reduced efficacy of alcohol metabolism leading to accumulation of highly toxic and carcinogenic acetaldehyde. It can induce unpleasant "Asian flush syndrome" and associate with increased risk of cancers. However, to date, little is known about ALDH2 genotypes in relation to the postoperative prognosis of hepatocellular carcinoma (HCC). Methods: From 2002 to 2012, 419 HCC patients receiving surgical resection of HCC were enrolled for ALDH2-rs671 genotyping and outcome correlation. Results: Of the patients included, 202 were ALDH2-rs671 "GG" (wild type) and 217 were mutant (defective) "AA" + "GA" genotype. Kaplan-Meier analysis indicated that "GG" genotype significantly associated with shorter metastasis-free (P = 0.034) and overall (P = 0.005) survival, but not recurrence-free survival (P = 0.281). Univariate followed by multivariate Cox proportional hazard analysis showed that "GG" genotype was an independent clinical predictor for shorter time-to-distant metastasis (adjusted P = 0.019) and shorter overall survival (adjusted P = 0.001). Subgroup analysis showed that in patients with negative hepatitis B surface antigen, Edmonson's histology grade < 3, and aspartate transaminase > alanine transaminase, the ALDH2-rs671-GG genotype was associated with both shorter time-to-metastasis and shorter overall survival. Conclusions: HCC patients carrying a defective allele of ALDH2 had a favorable postoperative outcome.

International Journal of Molecular Sciences, 2019

Several physiological processes, including cellular growth, embryonic development, differentiatio... more Several physiological processes, including cellular growth, embryonic development, differentiation, metabolism and proliferation, are modulated by genomic and nongenomic actions of thyroid hormones (TH). Several intracellular and extracellular candidate proteins are regulated by THs. 3,3,5-Triiodo-L-thyronine (T3) can interact with nuclear thyroid hormone receptors (TR) to modulate transcriptional activities via thyroid hormone response elements (TRE) in the regulatory regions of target genes or bind receptor molecules showing no structural homology to TRs, such as the cell surface receptor site on integrin αvβ3. Additionally, L-thyroxine (T4) binding to integrin αvβ3 is reported to induce gene expression through initiating non-genomic actions, further influencing angiogenesis and cell proliferation. Notably, thyroid hormones not only regulate the physiological processes of normal cells but also stimulate cancer cell proliferation via dysregulation of molecular and signaling pathway...

Hepatology communications, 2018

Metabolic risk factors, such as obesity, fatty liver, high lipidemia, and diabetes mellitus are a... more Metabolic risk factors, such as obesity, fatty liver, high lipidemia, and diabetes mellitus are associated with increased risk for nonviral hepatocellular carcinoma (HCC); however, few nonviral HCC studies have stratified patients according to underlying etiologies. From 2005 to 2011, 3,843 patients with HCC were recruited into the Taiwan Liver Cancer Network. Of these patients, 411 (10.69%) who were negative for hepatitis B virus (HBV), surface antigen, HBV DNA, and anti-hepatitis C virus (HCV) antibody were classified as non-HBV non-HCV (NBNC)-HCC. Detailed clinical analyses of these patients were compared with age- and sex-matched patients with HBV-HCC or HCV-HCC for the associated metabolic risk factors. For this comparison, 420 patients with HBV-HCC and 420 patients with HCV-HCC were selected from the 3,843 patients with HCC. Multivariate analyses showed fatty liver (by echography), high triglyceride levels (>160 mg/dL), and diabetes mellitus history to be significantly asso...

Neoplasia (New York, N.Y.), Jan 28, 2017

Thyroid hormone, 3,3',5-triiodo-l-thyronine (T3), mediates several physiological processes, i... more Thyroid hormone, 3,3',5-triiodo-l-thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation and cell proliferation, via binding to its nuclear thyroid receptors (TR). Previous microarray and Chromatin immunoprecipitation (ChIP)-on-ChIP analyses have revealed that interferon-stimulated gene 20 kDa (ISG20), an exoribonuclease involved in the antiviral function of interferon, is up-regulated by T3 in HepG2-TR cells. However, the underlying mechanisms of ISG20 action in tumor progression remain unknown to date. Here, we verified induction of ISG20 mRNA and protein expression by T3 in HepG2-TR cells. Based on the ChIP-on-ChIP database, potential thyroid hormone responsive element of the ISG20 promoter region was predicted, and the result confirmed with the ChIP assay. Functional assays showed that forced expression of ISG20 leads to significant promotion of metastasis and angiogenesis, both in vitro and in vivo. Furthermore, t...

Scientific Reports, 2017

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previo... more Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P < 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent pre...

International journal of cancer, 2017

NEK2 (NIMA-related expressed kinase 2) is a serine/threonine centrosomal kinase that acts as a cr... more NEK2 (NIMA-related expressed kinase 2) is a serine/threonine centrosomal kinase that acts as a critical regulator of centrosome structure and function. Aberrant NEK2 activities lead to failure in regulating centrosome duplication. NEK2 overexpression promotes tumorigenesis and is associated with poor prognosis in several cancers. Increased NEK2 expression during the late pathological stage has been detected in the Oncomine liver dataset and hepatocellular carcinoma (HCC) specimens. Elevated NEK2 protein is associated with poor overall survival in patients with HCC. However, the precise roles and mechanisms of NEK2 in liver cancer progression remain largely unknown. An earlier functional study revealed that NEK2 mediates drug resistance (cisplatin or lipo-doxorubicin) via expression of an ABCC10 transporter. Active angiogenesis and metastasis underlie the rapid recurrence and poor survival of HCC. Results from the current study showed that NEK2 mediates tumor growth, metastasis and a...

Hepatology (Baltimore, Md.), Jan 12, 2017

Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycoly... more Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of Taurine upregulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion and glycolysis via suppression of miR-455-3p. MiR-455-3p, which is transcriptionally repressed by p21, directly targets the 3'-untranslated region (UTR) of AMP-activated protein kinase subunit beta 2 (AMPKβ2). The TUG1/miR-455-3p/AMPKβ2 axis regulates cell growth, metastasis and glycolysis through regulation of Hexokinase 2 (HK2). TUG1 is clearly associated with HK2 overexpression and unfavorable prognosis in HCC patients. Our data collectively highlight that novel regulatory associations among TUG1, miR-455-3...

Scientific reports, Mar 31, 2017

With the availability of potent antiviral therapies, complete suppression of hepatitis B virus (H... more With the availability of potent antiviral therapies, complete suppression of hepatitis B virus (HBV) replication and total eradication of hepatitis C virus (HCV) can now be achieved. Despite these advances, hepatocellular carcinoma (HCC) still develops in a substantial proportion of cirrhotic patients, suggesting that host factors remain critical. Dysregulation of miRNAs is noted in many cancers, and circulating miRNAs can be readily assayed. In this study, we aimed to develop a circulating miRNA signature to assess the risk of HCC in cirrhotic patients. We first discovered that HBV- and HCV-related cirrhotic patients had distinguishable circulating miRNA profiles. A cohort of 330 cirrhotic patients was then compared against a cohort of 42 early HCC patients with complete remission. A score comprising 5 miRNAs and a binary etiology variable was established that was capable of differentiating between these two groups (AUC = 72.5%, P < 0.001). The 330 cirrhotic patients were furthe...

Anticancer research, Jun 1, 2017

Background /Aim: Reticulon 3 (RTN3), resides predominantly in the endoplasmic reticulum and has o... more Background /Aim: Reticulon 3 (RTN3), resides predominantly in the endoplasmic reticulum and has opposite regulatory effects on Hepatitis C virus (HCV) replication through interacting with NS5A and NS4B proteins. This study aimed to unravel the actual effect of RTN3 on HCV replication. A total of 115 HCV-related hepatocellular carcinoma patients receiving hepatectomy was enrolled in this study. The hepatic HCV RNA and RTN3 protein levels in the non-cancerous liver tissues were examined for clinical analysis. Of the 115 patients, 16 (11.5%) were occult HBV infection (positive for tissue HBV DNA. Univariate followed by multivariate analysis revealed that intrahepatic RTN3 levels were independently associated with higher HCV viral load (p=0.018) and HCV genotype 1 (p=0.017). Multivariate analysis revealed that HCV genotype 1, tumor size, albumin and aspartate transaminase associated with a shorter recurrence-free survival (p<0.05). Higher intrahepatic RTN3 levels independently correl...

Oncology Letters, 2017

Cholangiocarcinoma is a rare, sporadic and aggressive type of cancer. The genetic basis of cholan... more Cholangiocarcinoma is a rare, sporadic and aggressive type of cancer. The genetic basis of cholangiocarcinoma remains poorly understood. The present study investigated the prognostic role of the N-acetylgalactosaminyltransferase 14 (GALNT14)-rs9679162 genotype, an effective therapeutic response predictor for hepatocellular carcinoma in patients with cholangiocarcinoma receiving surgical resection. A cohort of patients with intrahepatic or perihilar cholangiocarcinoma (n=112) were retrospectively recruited. Of these patients, 31.3, 49.1 and 19.6% had GALNT14 'TT', 'TG' and 'GG' genotypes, respectively. The patient's genotype distributions did not deviate significantly from those of the ethnic reference cohorts, HapMap-Chinese Han Beijing and Chinese Han Metropolitan Denver. The genotype 'TT' was associated with unfavorable overall survival in univariate analysis (P=0.023). Furthermore, two tumor characteristics, perineural and vascular invasion, were independently associated with unfavorable overall survival (P=0.001 and P=0.002, respectively). The 'TT' genotypes were independently associated with two known predictors of unfavorable prognosis, perineural invasion (P=0.035) and lymph node metastasis (P=0.005) in a multivariate linear regression analysis. When compared with the two reference genotype cohorts, the 'TT' genotype was significantly higher in patients with perineural invasion (P=0.049, Beijing cohort; P=0.034, Denver cohort). Similar enrichment of the 'TT' genotype was also revealed in patients with lymph node metastasis (P=0.046, Beijing cohort; P=0.032 Denver cohort). In conclusion, the GALNT14-rs9679162 'TT' genotype was associated with perineural invasion and lymph node metastasis, as well as unfavorable overall survival in patients with resected cholangiocarcinoma.

World Journal of Gastroenterology, 2017

Author contributions: Hsieh AR and Tai DI contributed equally; Hsieh AR, Fann CSJ and Hsu CL cont... more Author contributions: Hsieh AR and Tai DI contributed equally; Hsieh AR, Fann CSJ and Hsu CL contributed to the statistical analysis; Tai DI contributed to developing the study protocol, interpreting the data, and writing the manuscript; Yeh CT contributed to HBV DNA and HBV genotyping assays; Lin HC, Wan SY and Tai J contributed to carried out the survey and collecting the data; Chen YC and Lin SM contributed to collecting the cases.

Autophagy, 2016

Recent studies have demonstrated a critical association between disruption of cellular thyroid ho... more Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showed that disruption of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy-related 7) via adeno-associated virus (AAV) vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death-associated protein kinase 2; a serine/threonine protein kinase), which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from DENinduced hepatotoxicity or carcinogenesis.

Hepatobiliary surgery and nutrition, 2014

Osteopontin (OPN) is a growth regulatory protein for hepatocellular carcinoma (HCC) and a potent ... more Osteopontin (OPN) is a growth regulatory protein for hepatocellular carcinoma (HCC) and a potent chemoattractant for macrophages. Zhu and colleagues recently reported significant clinical associations between poor postoperative prognosis and the concurrent detection of tumoral OPN expression and peritumoral macrophage (PTM) infiltration. An in-depth understanding on the complex interaction between tumoral OPN and macrophage-infiltrated microenvironment opens new doors to novel anticancer treatments.

Anticancer research, 2011

Since Rho-mediated signaling can regulate liver cancer cell proliferation, amino acid sequence ch... more Since Rho-mediated signaling can regulate liver cancer cell proliferation, amino acid sequence changes of its downstream targets, actins, might alter the properties of cell growth. Here, we investigated the function of a novel class of actins, named κ-actins, in hepatocellular carcinoma (HCC). Alexander cells overexpressing an HCC-derived κ-actin (Alex-κ cells) were established to study growth property changes. κ-actin expression was also determined in tumor and noncancerous tissues from 72 HCC patients. Survival analysis was conducted to evaluate the prognostic predictive value of κ-actin expression. Phylogenetic analysis showed that κ-actin sequences constituted 94.7% and 17.6% of actin transcripts in Alex-κ and naive Alexander cells, respectively. Alex-κ cells exhibited serum-independent cell growth with increased anchorage-independent colony formation and BrdU incorporation upon serum deprivation. Cox proportional hazard analysis showed that κ-actin expression in both cancerous ...

Cancer research, 2003

Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy. A few clinical trials h... more Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy. A few clinical trials have shown that the cytidine analogue gemcitabine appears to have antitumor activity for HCC, but the overall survival times remain to be improved. In this study, we examined the synergistic effect of adenovirus type 5 E1A (E1A) and gemcitabine on HCC and found that E1A sensitized J5, J7, Huh7, and HepG2 HCC cells to gemcitabine. To further study the E1A-mediated chemosensitization, we established stable cell lines that expressed the E1A gene and then examined whether E1A could have proapoptotic activity while expressed in HCC cells. Our results clearly showed that E1A sensitized HCC cells to gemcitabine through induction of apoptosis. To study the underlying mechanism, we tested nuclear factor (NF)-kappaB activity and found that NF-kappaB was activated in HCC cells treated with gemcitabine but not in HCC cells that expressed E1A. Occurrence of apoptosis entails cleavage of poly (ADP-ribo...

Oncology Letters, 2014

A GALNT14 single nucleotide polymorphism, rs9679162, has recently been found to be capable of pre... more A GALNT14 single nucleotide polymorphism, rs9679162, has recently been found to be capable of predicting chemotherapy responses in patients with far-advanced hepatocellular carcinoma (HCC). In the present study, a novel assay was designed and genotyping was performed on 244 surgically removed liver tissues. This assay employed two polymerase chain reaction (PCR)-generated restriction enzyme sites to simultaneously determine the genotypes of two adjacent single nucleotide polymorphisms (SNPs), rs9679162 and rs6752303, on the GALNT14 gene. Genotypes determined by this assay reached 100% concordance with those detected by the direct sequencing method. Clinical analysis showed that the TT genotype of rs9679162 was lower in percentage among patients with virus-originated HCC compared with those with non-viral HCC (22.57 vs. 47.06%, respectively; P=0.023). The proportion of the TT genotype in the 244 HCC patients (24.18%) did not deviate significantly from those of two public-domain (HapMap) Chinese cohorts from Denver, Colorado, USA (28.44%) and Beijing, China (30.15%) (P>0.05). The proportion of the TT genotype was significantly higher in Japanese and African populations (42.11-54.55%; P<0.0001) but significantly lower in an Italian cohort (7.84%; P=0.0004). In conclusion, the novel PCR-generated double restriction enzyme sites method could correctly determine the genotypes of two target SNPs in GALNT14 in liver tissues. The TT genotype was associated with the non-viral etiology of HCC. A marked variation in ethnicity was found for the distribution of this genotype.

Biomedical Journal, 2015

Background: Hepatitis B virus (HBV) infection is one of the infections with a highest prevalence ... more Background: Hepatitis B virus (HBV) infection is one of the infections with a highest prevalence in Taiwan. The most important marker is hepatitis B surface antigen (HBsAg). Using the new generation of HBsAg quantitative assay, HBsAg level may have good correlation with viral activity during different phases of chronic hepatitis B virus infection. This study was conducted to compare two assays of HBsAg level to find if the same results are obtained in HBsAg quantification in treatment-naïve and on-treatment chronic hepatitis B patients. Methods: Between March 2012 and June 2012, 90 patients with chronic hepatitis B (68 males and 22 females) were assessed using Abbott Architect HBsAg QT and Roche Elecsys HBsAg II assay. HBV DNA was detected by Roche COBAS TaqMan instrument. Results: HBsAg level measured with Elecsys and Architect assays correlated well in untreated patients (n = 53, γ s = 0.997) and on-treatment patients (n = 37, γ s = 0.988). Bland-Altman analyses of the discrepancies in HBsAg levels showed a bias of −4.2% in untreated patients and −6.2% in on-treatment patients. Patients with HBeAg-postive chronic hepatitis B had higher HBsAg level than the ones who were HBeAg negative, and both showed statistical differences. Further, HBV DNA concentration analysis also showed higher viral concentration in HBeAg-positive patients, but it revealed no statistical difference. Conclusions: There is a significant correlation between Abbott Architect HBsAg QT assay and Roche Elecsys HBsAg II assay. Moreover, HBsAg quantification may potentially provide complementary information about the deduction of the natural course in chronic hepatitis B infection.

Oncology Reports, 2012

The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a dual-specificity phos... more The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a dual-specificity phosphatase that dephosphorylates Cdk2 and inhibits cell cycle progression. The overexpression of KAP has been found in breast, prostate and renal cell carcinomas. However, the role of KAP in hepatocellular carcinoma (HCC) remains unclear. Therefore, the aim of this study was to investigate the expression of KAP in HCC and elucidate its role in tumorigenesis. HCC tissues from 117 patients undergoing surgical resection were collected for western blot analysis and immuno histochemichal analysis to establish clinical correlation. The antisense-mediated inhibition of KAP expression was performed in Huh-7 cell lines for tumorigenicity and growth regulation experiments. Clinicopathological analysis indicated that KAP was overexpressed in HCC tissue from alcoholic patients (P<0.001). It was significantly overexpressed in patients with a tumor number of <3 (P=0.0271), suggesting the potential role of KAP in tumorigenesis during early-stage alcohol-related HCC. Additionally, the antisense-mediated inhibition of KAP in Huh-7 HCC cells interfered with cell cycle progression, decreased cell proliferation, reduced the colony-forming ability of the cells and increased apoptosis. Tumorigenicity experiments showed that the KAP knockdown in Huh-7 cells generated smaller tumors in nude mice compared with the mock controls (P=0.018). In the cells in which KAP had been knocked down, the physical interaction between KAP and Cdk2 significantly increased, despite the reduced expression levels of KAP. The phosphorylation of cell proliferation and apoptosis-associated proteins, including phosphatase and tensin homolog (PTEN), glycogen synthase kinase (GSK), p44/42 and Akt, was decreased. Therefore, it can be concluded that KAP is overexpressed in alcohol-related HCC. The antisense-mediated knockdown of KAP in Huh-7 cells decreased cell proliferation, reduced the colony-forming ability of the cells, interfered with cell cycle progression and suppressed xenograft tumor formation, partly through enhanced KAP and Cdk2 interaction.