title: RASSF10 is Epigenetically Inactivated and Suppresses Cell Proliferation and Induces Cell Apoptosis by Activating the p53 Signalling Pathway in Papillary Thyroid Carcinoma Cancer.
abstract: OBJECTIVE
  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.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: Wendy
authors.initials: W
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Jin
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yu
authors.forename: Xiping
authors.initials: X
authors.lastname: Xin
mesh_terms: D000328:Adult; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; C548440:RASSF10 protein, human; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein
keywords: Apoptosis; Papillary Thyroid Carcinoma; RASSF10; p53 Signalling Pathway