4.1 Article

Expression and significance of miRNA-21 and BTG2 in lung cancer

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TUMOR BIOLOGY
卷 34, 期 6, 页码 4017-4026

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SPRINGER
DOI: 10.1007/s13277-013-0992-8

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Lung cancer; miRNA-21; BTG2; Cyclin D1

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This study investigates the expression of micro-ribonucleic acid-21 (miRNA-21) and B cell translocation gene 2 (BTG2) in lung cancer cells. We examined the impact of miRNA-21 on biological characteristics of lung cancer cells, such as growth, proliferation, apoptosis, and invasion. The expression of miRNA-21 and BTG2 protein in lung cancer cell lines (A549, HCC827, NCI-H292, and 95-D) was examined using quantitative reverse transcription-polymerase chain reaction and Western blot analysis, respectively. Subsequently, the regulatory role of miRNA-21 on BTG2 was explored by inhibiting miRNA-21 expression in 95-D cells using miRNA-21-antisense oligonucleotides (miRNA-21 ASO). The impact of miRNA-21 on the biological characteristics of 95-D cells was further studied using methylthiazol tetrazolium assays, flow cytometry, and Transwell invasion chamber assays. The impact of miRNA-21 on the expression of cyclin D1, caspase-3, and matrix metalloprotease-9 (MMP9) was also studied. miRNA-21 expression was significantly higher in lung cancer cell lines (A549, HCC827, NCI-H282, and 95-D) than that in normal human bronchial epithelial cells (HBE; p < 0.05). The pattern of BTG2 protein expression was exactly the opposite of miRNA-21 expression in lung cancer cells. BTG2 was highly expressed in HBE cells and was expressed at very low levels in lung cancer cell lines (A549, HCC827, NCI-H292, and 95-D). High miRNA-21 expression may inhibit BTG2 protein expression, whereas the inhibition of miRNA-21 expression may promote BTG2 protein expression in 95-D cells. Cell viability and invasion of 95-D cells were significantly lower in the miRNA-21 ASO-transfected group than that in the control ASO-transfected group and untransfected group (p < 0.05). The number of apoptotic cells was significantly higher in the miRNA-21 ASO-transfected group than that in the control ASO-transfected and untransfected groups (p < 0.05). The expression level of cyclin D1 and MMP9 in 95-D cells was significantly lower in the miRNA-21 ASO-transfected group than in the control ASO-transfected and untransfected groups (p < 0.05). Meanwhile, caspase-3 expression was significantly higher in the miRNA-21 ASO-transfected group than that in the control ASO-transfected and untransfected groups (p < 0.05). miRNA-21 overexpression may inhibit the BTG2 gene in lung cancer cells. miRNA-21 may promote cell proliferation and invasion and inhibit cell apoptosis in 95-D cells.

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