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Article ; Online: Actin-like Protein 6A Expression Correlates with Cancer Stem Cell-like Features and Poor Prognosis in Ovarian Cancer.

Chen, Po-Ming / Wong, Chui-Nguk / Wong, Chui-Na / Chu, Pei-Yi

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Ovarian cancer has the highest mortality rate among gynecological cancers, often diagnosed at the late stage and lacking an effective targeted therapy. Although the study of malignant features of cancer, considered to be cancer stem cells (CSCs), is ... ...

Abstract	Ovarian cancer has the highest mortality rate among gynecological cancers, often diagnosed at the late stage and lacking an effective targeted therapy. Although the study of malignant features of cancer, considered to be cancer stem cells (CSCs), is emerging, the aim of this study was to predict and explore the possible mechanism and clinical value of genetic markers in the development of ovarian cancer from a combined database with CSCs features. The common differentially expressed genes (DEGs) were selected in GSE185833 and GSE176246 datasets from the Gene Expression Omnibus (GEO). The GSE185833 dataset was created to reveal gene expression profiles of peritoneal metastasis tissues using single-cell sequencing, and the GSE176246 dataset was determined from gene expression profiles of chemotherapy-refractory ovarian cancer cell lines compared with ovarian cancer cell lines by RNA-seq analysis. By analyzing the correlation between common DEGs and prognosis of ovarian cancer and its possible pathways and functions were predicted by The Cancer Genome Atlas (TCGA) database. The expression levels of 11 genetic markers were significantly elevated in highly invasive and chemoresistant ovarian cancer. The expression of Actin-like protein 6A (ACTL6A) was found to be correlated with survival prognosis, and the total survival time of the patients with high expression of ACTL6A was shorter than those with low expression. Gene set enrichment analysis (GSEA) showed that ACTL6A positively enriched the gene set of 'Cell cycle' and ACTL6A negatively enriched the gene set of focal adhesion. CP724714, a human epidermal growth factor receptor 2 (HER2) inhibitor, could serve as a therapeutic option when ACTL6A levels are high in ovarian cancer cells. The high expression of ACTL6A is a poor prognostic factor in ovarian cancer and may serve as an effective biomarker for predicting treatment-refractory, metastasis, and prognosis of patients with ovarian cancer. The use of HER2 inhibitors is a promising therapeutic strategy against chemoresistant ovarian cancer.
MeSH term(s)	Female ; Humans ; Actins/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; DNA-Binding Proteins/metabolism ; Genetic Markers ; Neoplastic Stem Cells/metabolism ; Ovarian Neoplasms/metabolism ; Transcription Factors/genetics ; Prognosis
Chemical Substances	Actins ; ACTL6A protein, human ; Chromosomal Proteins, Non-Histone ; DNA-Binding Proteins ; Genetic Markers ; Transcription Factors
Language	English
Publishing date	2023-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032016
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Article ; Online: Catalase Expression Is an Independent Prognostic Marker in Lung Adenocarcinoma.

Chen, Po-Ming / Huang, Yu-Han / Chen, Hsin-Hung / Chu, Pei-Yi

Anticancer research

2023 Volume 44, Issue 1, Page(s) 287–300

Abstract: Background/aim: Lung adenocarcinoma (LUAD) is the deadliest cancer, and approximately 20% of stage I LUAD cases recur after surgical resection due to its high intratumor heterogeneity. Reactive oxygen species (ROS) have been detected in LUAD and are ... ...

Abstract	Background/aim: Lung adenocarcinoma (LUAD) is the deadliest cancer, and approximately 20% of stage I LUAD cases recur after surgical resection due to its high intratumor heterogeneity. Reactive oxygen species (ROS) have been detected in LUAD and are involved in carcinogenesis and tumor progression. Here, a comprehensive analysis was performed to evaluate the effects of antioxidants on the prognosis of LUAD. Materials and methods: The Cancer Genome Atlas (TCGA) database was used to study the relationship of gene expression of different ROS-scavenging enzymes with the progression and prognosis of LUAD. Results: Using TCGA LUAD datasets, we found that catalase (CAT) expression was significantly down-regulated in LUAD tissues compared to normal tissues, CAT down-regulation differed significantly between different grades of LUAD, low CAT expression was independently correlated with a worse prognosis in LUAD, and the expression of the CAT gene was associated with an inhibition of the "cell cycle". A panel of LUAD cells (CL1-0, CL1-1, CL1-3, and CL1-5), which harbored mutated p53 (R248W), with gradually increasing invasiveness showed a gradual decrease in CAT expression. Silencing of CAT upregulated cell growth in A549 cells, which harbor wild-type p53 and show high CAT expression and was associated with an increase in the expression of BUB1B, PLK1, and PKMYT1. Finally, over 38% (186/490) of LUAD cases with a p53 mutation exhibited significantly lower CAT expression than those with wild-type p53. Conclusion: CAT expression is a potent favorable prognostic marker for LUAD and may represent a drug target.
MeSH term(s)	Humans ; Lung Neoplasms/pathology ; Prognosis ; Catalase/genetics ; Catalase/metabolism ; Tumor Suppressor Protein p53 ; Reactive Oxygen Species/metabolism ; Neoplasm Recurrence, Local ; Adenocarcinoma of Lung/pathology ; Membrane Proteins/metabolism ; Protein-Tyrosine Kinases/metabolism ; Protein Serine-Threonine Kinases/metabolism
Chemical Substances	Catalase (EC 1.11.1.6) ; Tumor Suppressor Protein p53 ; Reactive Oxygen Species ; PKMYT1 protein, human (EC 2.7.11.1) ; Membrane Proteins ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-12-30
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16811
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Article ; Online: SGK1 Target Genes Involved in Heart and Blood Vessel Functions in PC12 Cells.

Li, Yu-He / Sun, Chia-Cheng / Chen, Po-Ming / Chen, Hsin-Hung

Cells

2023 Volume 12, Issue 12

Abstract: Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the ... ...

Abstract	Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the cellular mechanisms and signaling pathways of SGK1 in neuronal cells. In this study, the SGK1 inhibitor GSK650394 is used to suppress SGK1 expression in PC12 cells using an in vitro neuroscience research platform. Comparative transcriptomic analysis was performed to investigate the effects of SGK1 inhibition in nervous cells using mRNA sequencing (RNA-seq), differentially expressed genes (DEGs), and gene enrichment analysis. In total, 12,627 genes were identified, including 675 and 2152 DEGs at 48 and 72 h after treatment with GSK650394 in PC12 cells, respectively. Gene enrichment analysis data indicated that SGK1 inhibition-induced DEGs were enriched in 94 and 173 genes associated with vascular development and functional regulation and were validated using real-time PCR, Western blotting, and GEPIA2. Therefore, this study uses RNA-seq, DEG analysis, and GEPIA2 correlation analysis to identify positive candidate genes and signaling pathways regulated by SGK1 in rat nervous cells, which will enable further exploration of the underlying molecular signaling mechanisms of SGK1 and provide new insights into neuromodulation in cardiovascular diseases.
MeSH term(s)	Animals ; Rats ; Benzoates/pharmacology ; PC12 Cells ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction
Chemical Substances	2-cyclopentyl-4-(5-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl)-benzoic acid (56887611DJ) ; Benzoates ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; serum-glucocorticoid regulated kinase (EC 2.7.11.1)
Language	English
Publishing date	2023-06-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12121641
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Article ; Online: Translocation of Methionine Adenosyl Transferase MAT2A and Its Prognostic Relevance for Liver Hepatocellular Carcinoma.

Chu, Pei-Yi / Chou, Dev-Aur / Chen, Po-Ming / Chiang, En-Pei Isabel

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Methionine adenosyl transferases (MATs) catalyze the synthesis of the biological methyl donor adenosylmethionine (SAM). Dysregulation of MATs has been associated with carcinogenesis in humans. We previously found that downregulation of ... ...

Abstract	Methionine adenosyl transferases (MATs) catalyze the synthesis of the biological methyl donor adenosylmethionine (SAM). Dysregulation of MATs has been associated with carcinogenesis in humans. We previously found that downregulation of the
MeSH term(s)	Humans ; Male ; Female ; Carcinoma, Hepatocellular/metabolism ; Liver Neoplasms/metabolism ; Prognosis ; S-Adenosylmethionine/metabolism ; Transferases ; Methionine Adenosyltransferase/metabolism
Chemical Substances	S-Adenosylmethionine (7LP2MPO46S) ; Transferases (EC 2.-) ; Methionine Adenosyltransferase (EC 2.5.1.6) ; MAT2A protein, human (EC 2.5.1.6)
Language	English
Publishing date	2023-05-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24109103
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Article ; Online: Association of metallothionein 2A rs10636 with low mean corpuscular volume (MCV), low mean corpuscular haemoglobin (MCH) in healthy Taiwanese.

Chen, Rong-Fu / Chen, Po-Ming / Pan, Chau-Shiung / Huang, Chieh-Cheng / Chiang, En-Pei Isabel

Scientific reports

2023 Volume 13, Issue 1, Page(s) 1292

Abstract: Human metallothionein-2A (MT2A) protein participates in metal homeostasis, detoxification, oxidative stress reduction, and immune defense. It decreases heavy metal ions and reactive oxygen species (ROS) during injury of cells and tissues. The single ... ...

Abstract	Human metallothionein-2A (MT2A) protein participates in metal homeostasis, detoxification, oxidative stress reduction, and immune defense. It decreases heavy metal ions and reactive oxygen species (ROS) during injury of cells and tissues. The single nucleotide polymorphisms at the MT2A gene have been associated in various human diseases including cancer. The current study aimed to elucidate associations between MT2A genotypes with the clinical, biochemical, and molecular characteristics that potentially related to lowered MT2A ex-pression. One hundred and forty-one healthy Taiwanese subjects were enrolled from Changhua Show-Chwan Memorial Hospital. Clinical, biochemical and molecular characteristics including the frequent minor allele SNPs, rs28366003 and rs10636, within the MT2A gene were determined. The genotype distribution of MT2A rs10636 fits the Hardy-Weinberg equilibrium. The significant associations with gradually decline of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were identified with MT2A rs10636 and rs28366003 using analysis of variance (ANOVA) with Tukey's analysis as a post hoc test. We further validated the correlations between the expressions of genes in erythropoiesis, cholesterol synthesis, platelet synthesis, insulin with MT2A using the web-based Gene Expression Profiling Interactive Analysis (GEPIA) databases. The results revealed that hypoxia-inducible factor 1α (HIF-1α), erythropoietin (EPO), lipoprotein lipase (LPL), and lecithin-cholesterol acyltransferase (LCAT) mRNA ex-pression are significantly correlated with MT2A mRNA expression. In conclusion, these results suggested that genetic variations of MT2A rs10636 and rs28366003 might be an important risk factor for erythropoiesis in the Taiwanese general population.
MeSH term(s)	Humans ; Alleles ; Erythrocyte Indices ; Genotype ; Metallothionein/genetics ; Metals, Heavy/metabolism ; Erythropoiesis ; Polymorphism, Single Nucleotide ; Taiwan
Chemical Substances	Metallothionein (9038-94-2) ; Metals, Heavy ; MT2A protein, human
Language	English
Publishing date	2023-01-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-27304-6
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Article: miR-622 Increases miR-30a Expression through Inhibition of Hypoxia-Inducible Factor 1α to Improve Metastasis and Chemoresistance in Human Invasive Breast Cancer Cells.

Cheng, Chun-Wen / Liu, Yu-Fan / Liao, Wen-Ling / Chen, Po-Ming / Hung, Yueh-Tzu / Lee, Huei-Jane / Cheng, Yu-Chun / Wu, Pei-Ei / Lu, Yen-Shen / Shen, Chen-Yang

Cancers

2024 Volume 16, Issue 3

Abstract: Hypoxia-inducible factor 1α (HIF-1α) plays a pivotal role in the survival, metastasis, and response to treatment of solid tumors. Autophagy serves as a mechanism for tumor cells to eliminate misfolded proteins and damaged organelles, thus promoting ... ...

Abstract	Hypoxia-inducible factor 1α (HIF-1α) plays a pivotal role in the survival, metastasis, and response to treatment of solid tumors. Autophagy serves as a mechanism for tumor cells to eliminate misfolded proteins and damaged organelles, thus promoting invasiveness, metastasis, and resistance to treatment under hypoxic conditions. MicroRNA (miRNA) research underscores the significance of these non-coding molecules in regulating cancer-related protein synthesis across diverse contexts. However, there is limited reporting on miRNA-mediated gene expression studies, especially with respect to epithelial-mesenchymal transition (EMT) and autophagy in the context of hypoxic breast cancer. Our study reveals decreased levels of miRNA-622 (miR-622) and miRNA-30a (miR-30a) in invasive breast cancer cells compared to their non-invasive counterparts. Inducing miR-622 suppresses HIF-1α protein expression, subsequently activating miR-30a transcription. This cascade results in reduced invasiveness and migration of breast cancer cells by inhibiting EMT markers, such as Snail, Slug, and vimentin. Furthermore, miR-30a negatively regulates beclin 1, ATG5, and LC3-II and inhibits Akt protein phosphorylation. Consequently, this improves the sensitivity of invasive MDA-MB-231 cells to docetaxel treatment. In conclusion, our study highlights the therapeutic potential of inducing miR-622 to promote miR-30a expression and thus disrupt HIF-1α-associated EMT and autophagy pathways. This innovative strategy presents a promising approach to the treatment of aggressive breast cancer.
Language	English
Publishing date	2024-02-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16030657
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Article ; Online: LGR5 overexpression confers poor relapse-free survival in breast cancer patients.

Hou, Ming-Feng / Chen, Po-Ming / Chu, Pei-Yi

BMC cancer

2018 Volume 18, Issue 1, Page(s) 219

Abstract: Background: Cancer stem cells (CSCs) are believed to promote the malignant transformation of breast cancer via multiple signaling pathways, including the Wnt/β-catenin pathway. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has been ... ...

Abstract	Background: Cancer stem cells (CSCs) are believed to promote the malignant transformation of breast cancer via multiple signaling pathways, including the Wnt/β-catenin pathway. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has been identified as a CSC-associated Wnt-regulated target gene, but its clinical significance in the context of breast cancer remains elusive. Therefore, the purpose of this study was to investigate the clinical significance of the LGR5-β-catenin axis in breast cancer. Methods: Breast cancer tissue blocks from 126 patients were used to construct a tissue microarray (TMA). Histopathological and clinical data including age; tumor size; estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) level; tumor grade; lymph node (LN) status; and survival were obtained from the cancer registry database and patients' medical records. Tissue on the breast TMA was scored for LGR5 and β-catenin expression using semi-quantitative immunohistochemical (IHC) staining. We also analyzed LGR5 expression in cellular datasets available through ONCOMINE, a web-based cancer microarray database. Results: Immunohistochemical staining revealed that 58 tumors (46%) exhibited high LGR5 expression, whereas 56 tumors (47%) displayed high β-catenin expression. High levels of LGR5 expression were significantly associated with tumor size (p = 0.002), LN metastasis status (p = 0.044), and triple-negative breast cancer (p = 0.029), consistent with our findings from the ONCOMINE database. In addition, we also found that β-catenin -expressing breast cancers were positive correlated with HER2 overexpression. Finally, with respect to clinical outcomes, patients with high levels of LGR5-β-catenin axis expression exhibited poorer relapse-free survival (RFS) compared to patients with low levels of LGR5-β-catenin axis expression (p = 0.027). Conclusion: LGR5 overexpression was significantly associated with high T stage and LN metastasis status. High LGR5 expression was also associated with reduced RFS, indicating that LGR5 may represent a promising prognostic marker for breast cancer patients.
MeSH term(s)	Adult ; Aged ; Breast Neoplasms/diagnosis ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/physiology ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Up-Regulation ; Wnt Signaling Pathway ; beta Catenin/genetics ; beta Catenin/metabolism
Chemical Substances	CTNNB1 protein, human ; LGR5 protein, human ; Receptors, G-Protein-Coupled ; beta Catenin ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2018-02-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-018-4018-1
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Article: Cisplatin sensitivity mediated by NKX2-1 in lung adenocarcinoma is dependent on p53 mutational status via modulating TNFSF10 expression.

Chen, Ming-Jenn / Chen, Po-Ming / Wang, Lee / Shen, Ching-Ju / Chen, Chi-Yi / Lee, Huei

American journal of cancer research

2020 Volume 10, Issue 4, Page(s) 1229–1237

Abstract: NKX2-1 was shown to enhance cisplatin sensitivity in KRAS-mutated cells, but it conferred cisplatin resistance in EGFR-mutated lung adenocarcinoma cells. However, NKX2-1 as a dual role in tumor progression depended on p53 mutational status via modulation ...

Abstract	NKX2-1 was shown to enhance cisplatin sensitivity in KRAS-mutated cells, but it conferred cisplatin resistance in EGFR-mutated lung adenocarcinoma cells. However, NKX2-1 as a dual role in tumor progression depended on p53 mutational status via modulation of the NF-κB pathway. We hypothesized that NKX2-1 may confer cisplatin resistance in p53-mutated (p53-MT) lung adenocarcinoma cells but may enhance cisplatin sensitivity in wild-type (p53-WT) cells. In the present study, six p53-MT and -p53-WT cell lines were treated with various concentrations of cisplatin to calculate the inhibitory concentration of cisplatin for 50% cell viability (IC
Language	English
Publishing date	2020-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2589522-9
ISSN	2156-6976
ISSN	2156-6976
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Article: Expression of MTDH and IL-10 Is an Independent Predictor of Worse Prognosis in ER-Negative or PR-Negative Breast Cancer Patients.

Chu, Pei-Yi / Wang, Shin-Mae / Chen, Po-Ming / Tang, Feng-Yao / Chiang, En-Pei Isabel

Journal of clinical medicine

2020 Volume 9, Issue 10

Abstract: 1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by ... ...

Abstract	(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy.
Language	English
Publishing date	2020-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm9103153
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Article ; Online: Correction: Periostin promotes ovarian cancer metastasis by enhancing M2 macrophages and cancer-associated fibroblasts via integrin-mediated NF-κB and TGF-β2 signaling.

Lin, Sheng-Chieh / Liao, Yi-Chu / Chen, Po-Ming / Yang, Ya-Yu / Wang, Yi-Hsiang / Tung, Shiao-Lin / Chuang, Chi-Mu / Sung, Yu-Wen / Jang, Te-Hsuan / Chuang, Shuang-En / Wang, Lu-Hai

Journal of biomedical science

2023 Volume 30, Issue 1, Page(s) 54

Language	English
Publishing date	2023-07-12
Publishing country	England
Document type	Published Erratum
ZDB-ID	1193378-1
ISSN	1423-0127 ; 1021-7770
ISSN (online)	1423-0127
ISSN	1021-7770
DOI	10.1186/s12929-023-00948-w
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