title: miR-27a regulates the self renewal of the H446 small cell lung cancer             cell line in vitro.
abstract: Cancer growth is driven by cancer stem-like cells within a tumor, called             cancer stem cells (CSCs). Since miRNAs can regulate cell-fate decisions, we compared             miRNA expression in stem-like cells and differentiated cells from small cell lung             cancer (SCLC) cell lines to develop further understanding of the molecular mechanisms             involved in the pathogenesis of SCLC. First, SCLC stem-like cells were enriched             by isolating sphere-forming cells using a deﬁned serum-free medium. Further, microRNA             microarrays were used to measure the expression of 1212 miRNAs in sphere-forming             cells and parental cells. We found 86 miRNAs that were differentially expressed,             including 48 upregulated miRNAs and 38 downregulated miRNAs between sphere-forming             cells and parental cells. Among them, five downregulated miRNAs (let-7, miR-20,             21, 27a and 30b) and one upregulated miRNA (miR-149*) were selected for validation             in 3 sets of SCLC cell lines by qRT-RCR. The qRT-PCR analysis confirmed that all             six miRNAs were indeed differentially expressed. However, only miR-27a was consistently             downregulated in sphere-forming cells of all 3 cell lines. Antagonizing miR-27a             by inhibitor in parental cells enhanced proliferation, self renewal, and the proportion             of undifferentiated cells in vitro. The candidate miRNA and some miRNAs with same             seed sequence are predicted to have several target genes related to apoptosis,             cell proliferation and cell cycle. Our results suggest that downregulation of             miR-27a enhanced the stem-like properties of SCLC cells in vitro and may be critical             to maintaining a stem cell function in SCLC.
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Miao
authors.forename: Jiayin
authors.initials: J
authors.lastname: Li
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Qiu
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Li
authors.forename: Zhengyan
authors.initials: Z
authors.lastname: Wang
authors.forename: Yajing
authors.initials: Y
authors.lastname: Luan
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger