title: Mdig, a lung cancer-associated gene, regulates cell cycle progression through p27(KIP1).
abstract: Mineral dust-induced gene (mdig) can accelerate cell proliferation. The aim of this study is to investigate the mechanism by which mdig regulates cell proliferation. A549 cells were transfected with siRNA specifically targeting mdig. Cell proliferation and cell cycle progression were measured using MTT assay and cell cycle analysis, respectively. Furthermore, real-time reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was performed in A549 cells transfected with mdig siRNA to examine the expression levels of the cell cycle related genes such as p18(INK4c), p19(INK4d), p21(WAF/CIP1), p27(KIP1), p57(KIP2), cyclin D1, and cyclin E. To further explore the effect of mdig on p27(KIP1), the expression levels of total p27(KIP1) and its subtypes pT187-p27(KIP1) and pS10-p27(KIP1) were assessed by Western blotting. In vivo, Western blotting was performed to check the expression levels of mdig and p27(KIP1) in human lung cancer tissues, para-cancerous normal lung tissues, and para-bronchial stumps. Knockdown of mdig induced increases in p27(KIP1), both on mRNA and protein levels. Furthermore, the phosphorylation of p27(KIP1) at its Thr187 site was also inhibited. Importantly, in lung cancer tissues, upregulation of mdig expression accompanies with the downregulation of p27(KIP1) expression and in bronchial stump, vice versa. The data suggest that mdig-mediated inhibition of p27(KIP1) is important for cell proliferation and tumor formation and reveal therapeutic potential of p27(KIP1) for lung cancer.
authors: Department of Pulmonary Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.|Department of Pulmonary Medicine, The Fourth Hospital of China Medical University, Shenyang, 110032, China.
authors: Dan
authors: D
authors: Ma
authors: Department of Pulmonary Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.
authors: Dan
authors: D
authors: Guo
authors: Department of Pulmonary Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.
authors: Wei
authors: W
authors: Li
authors: Department of Pulmonary Medicine, The First Hospital of China Medical University, Shenyang, 110001, China. hwzhao2007@yahoo.com.
authors: Hongwen
authors: H
authors: Zhao
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis* / Q000235:genetics; D049308:Dioxygenases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D050760:Cyclin-Dependent Kinase Inhibitor p27; D049308:Dioxygenases; D056466:Histone Demethylases; C466777:RIOX2 protein, human
keywords: Cell cycle; Lung cancer; Mineral dust-induced gene; p27KIP1