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Enhancement of miR‐182 expression by Sp1 promotes lung cancer cell progression
Author(s) -
Hung JanJong
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.550.13
Subject(s) - carcinogenesis , microrna , lung cancer , sp1 transcription factor , biology , cancer research , foxo3 , cell growth , downregulation and upregulation , gene , promoter , regulation of gene expression , cancer , gene expression , genetics , medicine
Sp1 as a transcriptional factor regulates its target genes involved in cell growth, differentiation and apoptosis. Our previous study indicates that Sp1 accumulation is critical for lung tumorigenesis. Several microRNAs are also reported to be involved in cancer formation. Is there any relationship between Sp1 and mirRNA in lung tumorigenesis ? To address this issue, at first, we used the bioinformatics analysis to screen upstream flanking sequences of all intergenic miRNAs, and found that miR‐182 might be regulated by Sp1. Further study found that Sp1 could specific bind to promoter region of miR‐182 to regulate miR‐182 expression. Moreover, there is a well correlation between Sp1 level and miR‐182 level in lung cancer clinical specimens. By using three different databases of miRNA prediction screen the miR‐182 target genes. There are 161 genes were predicted to be regulated by miR‐182 possibly. Pathway analysis indicated that those genes major participated in regulation of cellular growth and proliferation. Overexpression of Sp1 decreased FOXO3 expression through miR‐182 regulation. Moreover, miR‐182 depletion delays mitotic transition by dysregulation of FOXO3 and inhibited lung cancer cells growth and tumor formation. Our data provide a mechanism of Sp1 regulated lung cancer progression through miR‐182 upregulation, thereby highlighting the importance of miRNAs biosynthesis in cancer.