The Preliminary Investigation On The Role And Molecular Mechanism Of B-Myb In Lung Cancer

B-Myb is one of the members of the classic Myb oncogene family, itplays an important role in many biological processes including cell cycleand tumorigenesis. However, its role and molecular mechanism in lungcancer remains unclear. Thus, this study was designed to solve this issue.(1) The expression and clinical significance of B-Myb in lung cancerAt first, we analyzed the expression level of B-Myb in normal lungtissue and lung cancer. The results showed that B-Myb is over-expressed inlung cancer and its overexpression is closely correlated to pathologicalgrade and clinical stage of lung cancer.Meanwhile, Two groups of lung cancer microarray data (GSE13213lung adenocarcinoma and squamous cell carcinoma of the lung GSE4573)were used to analyze the prognostic value of B-Myb in lung cancer. Theresults showed that high B-Myb expression is significantly correlated withpoor prognosis in lung cancer patients. Cox regression analysis showed thatB-Myb is an independent prognostic factor.(2) The effect of B-Myb gene overexpression and depletion on thecell proliferation, migration and invasion in lung cancer cells Lung cancer cell line H1299was used to establish B-Myb stableover-expressing and gene silencing cells, and then a series of experimentswere used to analyze the effects of B-Myb gene over-expression andsilencing on cell proliferation, invasive and migrative abilities in lungcancer cells. The results showed that B-Myb stable over-expressionincreased the percentage of cells in S phase, and significantly enhanced cellproliferation, colony formation, migration and invasion abilities. Depletionof B-Myb led to the increased percentage of cells in G2/M phase, andenhanced cell proliferation, colony formation, migrative and invasiveabilities. Those results suggested that the high expression of B-Myb in lungcancer cells facilitates the cell proliferation, migrative and invasive abilities,and consequently promotes the development and metastasis of lung cancer.(3) The effect of B-Myb stable overexpression and depletion ontranscription of downstream key target genesGiven that B-Myb functions as a transcription factor, which exerts itsbiological function mainly by regulating the expression of lots of targetgenes. Thus, quantitative RT-PCR was used to analyze the effect of B-Mybgene over-expression and silencing on the transcription of some importantcell cycle-and tumorigenesis-related genes. The results showed that B-Mybgene over-expression significantly up-regulated the transcription of cellcycle-related gene CCNA1and cell motility-related genes MMP1andTGF-β2. B-Myb depletion led to the downregulation of CCNA1, TGF-β 2and MMP1. These results suggested that B-Myb promoted theproliferation, invasive and migrative abilities through transactivating itsdownstream target genes such as CCNA1, TGF-β2and MMP1in lungcancer cells.Taken together, our study indicated that B-Myb is a novel geneinvolved in the tumorigenesis and development of lung cancer, B-Mybover-expression in lung cancer promots proliferation, migrative andinvasive abilities of lung cancer cells via transactivating its downstreamtarget genes such as CCNA1, TGF-β2and MMP1, and consequently leadto the development and metastasis in lung cancer.