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Let-7/miR-98 regulate Fas and Fas-mediated apoptosis

Genes & Immunity volume 12, pages 149–154 (2011)Cite this article

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Abstract

Fas is ubiquitously expressed on a variety of cells and triggers apoptosis, which have critical roles in the immune system. MicroRNAs (miRNAs) have been recently identified as regulators that modulate target gene expression and are involved in diverse biological processes, such as cell proliferation and apoptosis. This study was undertaken to investigate the contribution of miRNA in the regulation of Fas expression and Fas-mediated apoptosis. Bioinformatics analysis indicated that Fas was a potential target of let-7/miR-98 family. Indeed ectopic expression of let-7/miR-98 reduced, whereas knockdown of endogenous let-7/miR-98 increased the expression of Fas at both mRNA and protein levels. Let-7/miR-98 was verified to target Fas 3′ untranslated region directly by site-directed gene mutagenesis and reporter gene assay. More importantly, introduction of let-7/miR-98 could decrease the sensitivity to Fas-induced apoptosis. Furthermore, let-7/miR-98 expression was reduced in activation-induced cell death process, accompanied by increased expression of Fas. In conclusion, our study first demonstrated that let-7/miR-98 regulated Fas expression and the sensitivity of Fas-mediated apoptosis.

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Acknowledgements

This work was supported in part by the National High Technology Research and Development Program of China (863 Program; no. 2007AA02Z123), the National Basic Research Program of China (973 Program; no. 2007CB947900), the National Natural Science Funds for Distinguished young scholar (no. 81025016), the National Natural Science Foundation of China (no. 30700734, no. 30301026, no. 30971632), the Program of the Shanghai Commission of Science and Technology (no. 06JC14050, no. 07ZR14130, no. 08JC1414700) and Program of Shanghai Subject Chief Scientist (no. 07XD14021). We thank Bo Qu, Xiaoxia Qian, Xiang Miao and Haibo Zhou for helpful discussions, technical expertise and/or review of this manuscript.

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Author notes

  1. S Wang and Y Tang: These authors contributed equally to this work.

Authors and Affiliations

  1. Joint Molecular Rheumatology Laboratory of the Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiaotong University School of Medicine, Shanghai, China

    S Wang, Y Tang, H Cui, X Zhao, X Luo, W Pan, X Huang & N Shen

  2. Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Y Tang, H Cui, X Luo, W Pan & N Shen

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  1. S Wang
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Correspondence to Y Tang or N Shen.

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Wang, S., Tang, Y., Cui, H. et al. Let-7/miR-98 regulate Fas and Fas-mediated apoptosis. Genes Immun 12, 149–154 (2011). https://doi.org/10.1038/gene.2010.53

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