P3.42. Promoter methylation and protein expression of hMLH1 gene in oral cancer. Preliminary report

OBJECTIVE: The hMLH1 gene is one of the mismatch DNA repair genes. Inactivation of the hMLH1 gene has been implicated in the tumorigenesis of many types of human cancers. In most sporadic forms of human cancers, promoter hypermethylation is responsible for hMLH1 gene inactivation. Lack of hMLH1 protein expression has been found in a subset of head and neck squamous cell carcinomas (HNSCCs). The purpose of this study was to investigate whether promoter hypermethylation causes hMLH1 gene inactivation in HNSCCs. STUDY DESIGN: hMLH1 protein expression was determined by immunohistochemical staining in 62 cases, whereas hMLH1 gene promoter methylation was analyzed by methylation-sensitive restriction enzyme digestion, followed by polymerase chain reaction, in 35 cases of HNSCCs. RESULTS: Sixteen (26%) of 62 cases of HNSCCs showed near-complete loss of hMLH1 protein expression on immunohistochemical staining. Twelve (92%) of 13 cases that were negative for the hMLH1 protein displayed promoter hypermethylation, whereas 17 (77%) of 22 cases positive for the protein were free of promoter methylation. CONCLUSIONS: Promoter hypermethylation may be an important mechanism for hMLH1 gene inactivation in a subset of HNSCCs.

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Mechanism of MicroRNA-375 Promoter Methylation in Promoting Ovarian Cancer Cell Malignancy

Technology in Cancer Research & Treatment ◽

10.1177/1533033820980115 ◽

2021 ◽

Vol 20 ◽

pp. 153303382098011

Author(s):

Junjun Shu ◽

Ling Xiao ◽

Sanhua Yan ◽

Boqun Fan ◽

Xia Zou ◽

...

Keyword(s):

Ovarian Cancer ◽

Protein Expression ◽

Cell Lines ◽

Cell Invasion ◽

Promoter Methylation ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Gene Assay ◽

Cell Malignancy

Objective: Ovarian cancer (OC) ranks one of the most prevalent fatal tumors of female genital organs. Aberrant promoter methylation triggers changes of microRNA (miR)-375 in OC. Our study aimed to evaluate the mechanism of methylated miR-375 promoter region in OC cell malignancy and to seek the possible treatment for OC. Methods: miR-375 promoter methylation level in OC tissues and cells was detected. miR-375 expression in OC tissues and cell lines was compared with that in demethylated cells. Role of miR-375 in OC progression was measured. Dual-luciferase reporter gene assay was utilized to verify the targeting relationship between miR-375 and Yes-associated protein 1 (YAP1). Then, Wnt/β-catenin pathway-related protein expression was tested. Moreover, xenograft transplantation was applied to confirm the in vitro experiments. Results: Highly methylated miR-375 was seen in OC tissues and cell lines, while its expression was decreased as the promoter methylation increased. Demethylation in OC cells brought miR-375 back to normal level, with obviously declined cell invasion, migration and viability and improved apoptosis. Additionally, miR-375 targeted YAP1 to regulate the Wnt/β-catenin pathway protein expression. Overexpressed YAP1 reversed the protein expression, promoted cell invasion, migration and viability while reduced cell apoptosis. Overexpressed miR-375 in vivo inhibited OC progression. Conclusion: Our study demonstrated that demethylated miR-375 inhibited OC growth by targeting YAP1 and downregulating the Wnt/β-catenin pathway. This investigation may offer novel insight for OC treatment.

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APC promoter methylation and protein expression in hepatocellular carcinoma

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-007-0321-y ◽

2007 ◽

Vol 134 (5) ◽

pp. 579-589 ◽

Cited By ~ 29

Author(s):

Antal Csepregi ◽

Christoph Röcken ◽

Juliane Hoffmann ◽

Ping Gu ◽

Stephan Saliger ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Protein Expression ◽

Promoter Methylation

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Platyphyllenone Induces Autophagy and Apoptosis by Modulating the AKT and JNK Mitogen-Activated Protein Kinase Pathways in Oral Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22084211 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4211

Author(s):

Yen-Tze Liu ◽

Hsin-Yu Ho ◽

Chia-Chieh Lin ◽

Yi-Ching Chuang ◽

Yu-Sheng Lo ◽

...

Keyword(s):

Protein Kinase ◽

Oral Cancer ◽

Protein Expression ◽

Caspase 3 ◽

Therapeutic Option ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Dependent Manner ◽

Cancer Proliferation ◽

Mitogen Activated Protein

Platyphyllenone is a type of diarylheptanoid that exhibits anti-inflammatory and chemoprotective effects. However, its effect on oral cancer remains unclear. In this study, we investigated whether platyphyllenone can promote apoptosis and autophagy in SCC-9 and SCC-47 cells. We found that it dose-dependently promoted the cleavage of PARP; caspase-3, -8, and -9 protein expression; and also led to cell cycle arrest at the G2/M phase. Platyphyllenone up-regulated LC3-II and p62 protein expression in both SCC-9 and SCC-47 cell lines, implying that it can induce autophagy. Furthermore, the results demonstrated that platyphyllenone significantly decreased p-AKT and increased p-JNK1/2 mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner. The specific inhibitors of p-JNK1/2 also reduced platyphyllenone-induced cleavage of PARP, caspase-3, and caspase -8, LC3-II and p62 protein expression. These findings are the first to demonstrate that platyphyllenone can induce both autophagy and apoptosis in oral cancers, and it is expected to provide a therapeutic option as a chemopreventive agent against oral cancer proliferation.

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