title: Comparative profiling of miRNA expression of lung adenocarcinoma cells in two-dimensional and three-dimensional cultures.
abstract: Three-dimensional organotypic culture using reconstituted basement membrane matrix (rBM 3-D) is an invaluable tool to characterize morphogenesis of epithelial cells and to elucidate the tumor-modulating actions of extracellular matrix. microRNAs (miRNA) are a novel class of tumor modulating genes. A substantial amount of investigation of miRNAs in cancer is carried out using monolayer 2-D culture on plastic substratum, which lacks a consideration of the matrix-mediated regulation of miRNAs. In the current study we compared the expression of miRNAs in rBM 3-D and 2-D cultures of two lung adenocarcinoma cell lines. Our findings revealed a profound difference in miRNA profiles between 2-D and rBM 3-D cultures of lung adenocarcinoma cells. The rBM 3-D culture-specific miRNA profile was highlighted with higher expression of the tumor suppressive miRNAs (i.e., miR-200 family) and lower expression of the oncogenic miRNAs (i.e., miR-17-92 cluster and miR-21) than that of 2-D culture. Moreover, the expression pattern of miR-17, miR-21, and miR-200a in rBM 3-D culture correlated with the expression of their targets and acinar morphogenesis, a differentiation behavior of lung epithelial cells in rBM 3-D culture. Over-expression of miR-21 suppressed its target PTEN and disrupted acinar morphogenesis. In summary, we provide the first miRNA profile of lung adenocarcinoma cells in rBM 3-D culture with respect to acinar morphogenesis. These results indicate that rBM 3-D culture is essential to a comprehensive understanding of the miRNA biology in lung epithelial cells pertinent to lung adenocarcinoma.
authors.affiliation: Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Hong T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lin
authors.forename: Erik K
authors.initials: EK
authors.lastname: Flemington
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhuo
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Kantrow
authors.forename: Gilbert F
authors.initials: GF
authors.lastname: Morris
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Sullivan
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs