1. Academic Validation
  2. NFKB1-miR-612-FAIM2 pathway regulates tumorigenesis in neurofibromatosis type 1

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

  • In Vitro Cell Dev Biol Anim. 2019 Aug;55(7):491-500. doi: 10.1007/s11626-019-00370-3.
Meng Wang 1 Zengtao Wang 2 Xiaolei Zhu 2 Shibing Guan 2 Zhibo Liu 2
Affiliations

Affiliations

  • 1 Hand and Foot Surgical Center, Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China. MengMMM_Wang35@163.com.
  • 2 Hand and Foot Surgical Center, Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
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.

Keywords

FAIM2; MPNST; NF1; NFKB1; miR-612.

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