RASSF10 is Epigenetically Inactivated and Suppresses Cell Proliferation and Induces Cell Apoptosis by Activating the p53 Signalling Pathway in Papillary Thyroid Carcinoma Cancer

Autor: Wendy Wang, Zhuo Yu, Xiping Xin, Ji Jin, Cheng Fan
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Physiology
Apoptosis
lcsh:Physiology
Epigenesis
Genetic
0302 clinical medicine
Cell Movement
p53 Signalling Pathway
lcsh:QD415-436
RNA
Small Interfering
bcl-2-Associated X Protein
medicine.diagnostic_test
lcsh:QP1-981
Chemistry
Transfection
Middle Aged
Hedgehog signaling pathway
Blot
Gene Expression Regulation
Neoplastic
Proto-Oncogene Proteins c-bcl-2
Thyroid Cancer
Papillary
030220 oncology & carcinogenesis
Female
Plasmids
Signal Transduction
Adult
Cyclin-Dependent Kinase Inhibitor p21
Flow cytometry
lcsh:Biochemistry
03 medical and health sciences
Cell Line
Tumor
medicine
Humans
Thyroid Neoplasms
Cell Proliferation
Cell growth
Tumor Suppressor Proteins
Carcinoma
DNA Methylation
Papillary Thyroid Carcinoma
Carcinoma
Papillary
030104 developmental biology
Cell culture
Cancer research
RASSF10
Tumor Suppressor Protein p53
Wound healing
Zdroj: Cellular Physiology and Biochemistry, Vol 41, Iss 3, Pp 1229-1239 (2017)
ISSN: 1421-9778
1015-8987
Popis: Objectives: We aimed to confirm whether RASSF10 activated the p53 signalling pathway, thereby modulating cell proliferation, migration, invasion, and apoptosis in papillary thyroid carcinoma (PTC) cells. Methods: A total of 108 PTC tissue samples and normal adjacent tissues were obtained. RT-PCR and Western blotting analyses were performed to detect RASSF10 expression, and methylation levels of RASSF10 were estimated by methylation-specific PCR (MSP). We also detected the expression and methylation status of RASSF10 in both a human PTC cell line (K1) and a normal thyroid cell line (FRTL5). After transfection of cells with empty vector pcDNA3.1, pcDNA3.1-RASSF10, p53 siRNA and shRASSF10, Coulter counter, colony-formation, wound healing, Transwell and flow cytometry analyses were performed to examine the role of RASSF10 in cell proliferation, migration, invasion, and apoptosis. Finally, the expression of p53, p21, Bcl-2 and Bax were detected using Western Blotting analyses. Results: RASSF10 expression in PTC tissues was significantly lower and hyper-methylated compared to normal adjacent tissues. In addition, RASSF10 was significantly down-regulated and hyper-methylated in K1 cells compared to FRTL5 cells. In addition, suppressed proliferation and significantly induced apoptosis of K1 cells were observed after transfection with pcDNA3.1-RASSF10 (P < 0.05). Furthermore, RASSF10 activated the p53 signalling pathway and regulated the expression of p53, p21, Bcl-2 and Bax. Furthermore, p53 siRNA could antagonize the effects of RASSF10 in K1 cells. Conclusions: RASSF10 induces apoptosis in PTC cells by activating the p53 signalling pathway, indicating its role as a treatment target for PTC.
Databáze: OpenAIRE
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