MicroRNA‐494 suppresses cell proliferation and induces senescence in A549 lung cancer cells

Cell Proliferation - Tập 45 Số 1 - Trang 32-38 - 2012
Hiroaki Ohdaira1, Masaki Sekiguchi1, Kenichi Miyata1, Kenichi Yoshida1
1Department of Life Sciences, Meiji University, Kawasaki, Kanagawa, Japan

Tóm tắt

AbstractObjectives:  MicroRNAs (miRNAs) are small functional RNAs that regulate mRNAs for degradation or translational suppression. In the present study, we aimed to reveal functional importance of miRNA‐494 (miR‐494) in A549 human lung cancer cells.Materials and methods:  We established A549 cells that constitutively expressed miR‐494. Next, we sought to investigate insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) mRNA as an miR‐494 target. For this, we constructed a reporter plasmid bearing potential miR‐494 binding sequences derived from the 3′‐untranslated region (3′‐UTR) of IGF2BP1 mRNA in the 3′‐UTR of the luciferase gene.Results:  Through comparison between miR‐494 expressing cells and control cells, we revealed that miR‐494 suppressed cell proliferation and colony forming activity, and induced senescence. Reporter activity was inhibited by miR‐494. In addition, IGF2BP1 mRNA levels were down‐regulated in A549 cells that constitutively expressed miR‐494. IGF2BP1 has been shown to bind and suppress IGF2 mRNA, and this could be a reason why IGF2BP1 can regulate cell function. Therefore, we analysed IGF2 mRNA levels and revealed that IGF2 was up‐regulated in A549 cells that constitutively expressed miR‐494. Finally, elevated IGF2 mRNA levels in A549 cells that constitutively expressed miR‐494 were suppressed to basal level by an miR‐494 inhibitor.Conclusions:  Taken together, IGF2BP1 and its downstream target IGF2 could be a crucial axis for miR‐494 in regulation of the destiny of A549 cells.

Từ khóa


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Thông tin xuất bản

Cell Proliferation

Tập 45 Số 1

32-38

Thông tin tác giả