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NFKB1-miR-612-FAIM2 pathway regulates tumorigenesis in neurofibromatosis type 1

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Abstract

Neurofibromatosis type I (NF1) is a carcinoma mainly featured by malignant peripheral nerve sheath tumor (MPNST). Dysregulated microRNAs (miRNAs) play decisive roles in tumor initiation and development. Our study sought for the possible roles of miR-612 in NF1. RT-qPCR estimated the expression of nuclear factor kappa B subunit 1 (NFKB1), miR-612, and Fas apoptotic inhibitory molecule 2 (FAIM2) in NF1, separately. Cell proliferation and migration were detected by CCK-8 and transwell experiments. Cell apoptosis was measured via flow cytometry and detection of the expression and activity of caspase 3/8/9. Luciferase reporter, ChIP, and RIP assays testified the interplay between studied genes. Rescue and in vivo assays affirmed the whole mechanism of miR-612 in NF1. We indicated that miR-612 was significantly low in tumor tissues and cells. Mechanism experiments confirmed that miR-612 promotion repressed cell proliferation and migration, and induced cell apoptosis. Besides, NFKB1-regulated miR-612 targeted FAIM2. Spearman’s correlation analysis validated the correlation between each two genes. Finally, rescue and in vivo assays affirmed that miR-612 targeted FAIM2 to regulate cellular activities of NF1. The current investigation uncovered the molecular mechanism underlying miR-612 in NF1, establishing miR-612 as a novel therapeutic target for the treatment of NF1 patients.

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Acknowledgments

We sincerely thank all involvers in this research.

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Authors and Affiliations

  1. Hand and Foot Surgical Center, Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China

    Meng Wang, Zengtao Wang, Xiaolei Zhu, Shibing Guan & Zhibo Liu

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  1. Meng Wang
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  2. Zengtao Wang
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  3. Xiaolei Zhu
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  4. Shibing Guan
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  5. Zhibo Liu
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Correspondence to Meng Wang.

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Editor: Tetsuji Okamoto

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Wang, M., Wang, Z., Zhu, X. et al. NFKB1-miR-612-FAIM2 pathway regulates tumorigenesis in neurofibromatosis type 1. In Vitro Cell.Dev.Biol.-Animal 55, 491–500 (2019). https://doi.org/10.1007/s11626-019-00370-3

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  • DOI: https://doi.org/10.1007/s11626-019-00370-3

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