miR-27a regulates the self renewal of the H446 small cell lung cancer cell line in vitro
Autor: | Jiayin Li, Zhengyan Wang, Yajing Luan, Yajing Miao, Xiaofei Qiu, Yanlei Li |
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Rok vydání: | 2012 |
Předmět: |
Cancer Research
Lung Neoplasms Cellular differentiation Cell Fluorescent Antibody Technique Apoptosis In Vitro Techniques Biology Real-Time Polymerase Chain Reaction medicine.disease_cause Cancer stem cell Biomarkers Tumor Tumor Cells Cultured medicine Humans RNA Messenger Cell Proliferation Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Cell growth Gene Expression Profiling Cell Differentiation General Medicine Cell cycle Small Cell Lung Carcinoma Cell biology MicroRNAs medicine.anatomical_structure Oncology Neoplastic Stem Cells Stem cell Carcinogenesis A431 cells |
Zdroj: | Oncology Reports. 29:161-168 |
ISSN: | 1791-2431 1021-335X |
DOI: | 10.3892/or.2012.2095 |
Popis: | 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. |
Databáze: | OpenAIRE |
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