Browsing by Author "Yang, Muh-Hwa"

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DNA Methyltransferases Modulate Hepatogenic Lineage Plasticity of Mesenchymal Stromal Cells
(2017-07-11)
Lee, Chien-Wei
;
Huang, Wei-Chih
;
Huang, Hsien-Da
;
Huang, Yi-Hsiang
;
Ho, Jennifer H.
The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor beta 1 (TGF beta 1), which in turn controls hepatogenic differentiation and de-differentiation. In addition, a stepwise reduction in TGF beta 1 concentrations in culture media increases DNMT1 and decreases DNMT3 in primary hepatocytes (Heps) and confers Heps with multi-differentiation potentials similarly to MSCs. Hepatic lineage reversibility of MSCs and lineage conversion of Heps are regulated byDNMTs in response to TGF gamma 1. This previously unrecognized TGF beta 1-DNMTs-MSC-HD axis may further increase the understanding the normal and pathological processes in the liver, as well as functions of MSCs after transplantation to treat liver diseases.
Identification of a noncanonical function for ribose-5-phosphate isomerase A promotes colorectal cancer formation by stabilizing and activating beta-catenin via a novel C-terminal domain
(2018-01-01)
Chou, Yu-Ting
;
Jiang, Jeng-Kai
;
Yang, Muh-Hwa
;
Lu, Jeng-Wei
;
Lin, Hua-Kuo
Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5-phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80 patients' CRC tissues and paired nontumor tissues and protein levels, as well as a CRC tissue array, indicate RPIA is significantly elevated in CRC. RPIA modulates cell proliferation and oncogenicity via activation of beta-catenin in colon cancer cell lines. Unlike its role in PPP in which RPIA functions within the cytosol, RPIA enters the nucleus to form a complex with the adenomatous polyposis coli (APC) and beta-catenin. This association protects beta-catenin by preventing its phosphorylation, ubiquitination, and subsequent degradation. The C-terminus of RPIA (amino acids 290 to 311), a region distinct from its enzymatic domain, is necessary for RPIA-mediated tumorigenesis. Consistent with results in vitro, RPIA increases the expression of beta-catenin and its target genes, and induces tumorigenesis in gut-specific promotor-carrying RPIA transgenic zebrafish. Together, we demonstrate a novel function of RPIA in CRC formation in which RPIA enters the nucleus and stabilizes beta-catenin activity and suggests that RPIA might be a biomarker for targeted therapy and prognosis.
Prediction of Metastasis in Head and Neck Cancer from Computed Tomography Images
(2018-01-01)
Lo, Tzu-Yun
;
Wei, Pei-Yin
;
Yen, Chia-Heng
;
Lirng, Jiing-Feng
;
Yang, Muh-Hwa
The current medical method for determining whether the malignant tumor of the head and neck metastasizes to the lymph is to interpret the pathological section of the patient's lymph. This study proposes a support vector machine (SVM) based method Pred-Meta to predict metastasis of a malignant tumor from a patient's computed tomography (CT) image. Pred-Meta utilizes three feature types, including texture, morphology, and grayscale, and an optimal feature selection method cooperated with SVM. The data set consists of 75 samples from 70 patients in head and neck cancer provided by Taipei Veterans General Hospital of Taiwan with a record of lymphatic metastasis. Pred-Meta using leave-one-out cross-validation achieved 100% in predicting metastasis. The merit of the Pred-Meta method is its non-invasiveness and low cost. Auxiliary physicians screen out patients with high risk of diversion in the early stages to help plan treatment guidelines. The limitation of Pred-Meta suffers from the small number of training samples. It is expected that Pred-Meta would perform better in testing independent cohort when the number of training samples significantly increases.