title: Epigenetic regulation of miR-129-2 and its effects on the proliferation and invasion in lung cancer cells.
abstract: MicroRNAs (miRNAs) play a pivotal role in carcinogenesis. Dysregulation of miRNAs, both oncogenic miRNAs and tumour-suppressive miRNAs, is closely associated with cancer development and progression. The levels of miRNAs could be changed epigenetically by DNA methylation in the 5' untranslated region (UTR) of pre-mature miRNAs. To investigate whether DNA methylation alters the expression of miR-129 in lung cancer, we did DNA methylation assays and found that 5' UTR region of miR-129-2 gene was absolutely methylated in both A549 and SPCA-1 lung cancer cells, but totally un-methylated in 95-D cells. The expression of miR-129 was restored by 5-Aza-2'-deoxycytidine (DAC), a de-methylation agent, in both A549 and SPCA-1 cells, resulting in attenuated cell migration and invasion ability, and decreased protein level of NF-κB, which indicates the involvement of NF-κB pathway. To further illustrate the roles of miR-129 in lung tumourigenesis, we overexpressed miR-129 in lung cancer cells by transfection of miR-129 mimics, and found arrested cell proliferation at G2/M phase of cell cycle and inhibited cell invasion. These findings strongly suggest that miR-129 is a tumour suppressive miRNA, playing important roles in the development and progression of human lung cancer.
authors.affiliation: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
authors.forename: Haoli
authors.initials: H
authors.lastname: Wang
authors.affiliation: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Wen
authors.affiliation: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: He
authors.affiliation: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D012333:RNA, Messenger; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: DNA methylation; cell invasion; lung cancer; microRNA; valosin-containing protein