| 論文作者 |
Li, YH; Chung, MH; Aimaier, R; Wei, CJ; Wang, W; Ge, LL; Zhu, BY; Guo, ZZ; Wang, MY; Gu, YH; Zhang, HB; Li, QF; Wang, ZC |
| 摘要 |
Simple Summary Malignant peripheral nerve sheath tumours (MPNSTs) are highly aggressive and invasive peripheral soft-tissue sarcomas that typically develop in the context of neurofibromatosis type 1 (NF1). Compared with sporadic MPNSTs, patients with NF1-derived MPNSTs are younger and have a worse prognosis. The aim of our study is to further identify potential targets for the treatment of NF1-derived MPNSTs based on existing therapies. We found that the nuclear receptor corepressor 2 (NCOR2) could regulate ERK activation through the brain-derived neurotrophic factor (BDNF)/TrkB pathway, thereby affecting the growth of NF1-derived MPNSTs. This finding may provide new drug targets and combined drug therapy strategies for the clinical treatment of NF1-derived MPNSTs. (1) Background: malignant peripheral nerve sheath tumours (MPNSTs) are aggressive Schwann cell-derived sarcomas with dismal prognoses. Previous studies have shown that nuclear receptor corepressor 2 (NCOR2) plays a vital role in neurodevelopment and in various tumours. However, the impact of NCOR2 on the progression of MPNST remains unclear. (2) Methods: by GEO database, MPNST tissue microarray, and NF1-related tumour tissues and cell lines were used to explore NCOR2 expression level in the MPNSTs. The role and mechanism of NCOR2 in NF1-derived MPNSTs were explored by experiments in vivo and in vitro and by transcriptome high-throughput sequencing. (3) Results: NCOR2 expression is significantly elevated in NF1-derived MPNSTs and is associated with patient 10-year survival time. Knockdown of NCOR2 suppressed NF1-derived MPNST cell proliferation by blocking the cell cycle in the G0/G1 phase. Moreover, decreased NCOR2 expression could down-regulate MAPK signal activity through the BDNF/TrkB pathway. (4) Conclusions: our findings demonstrated that NCOR2 expression is significantly elevated in NF1-derived MPNSTs. NCOR2 knockdown can inhibit NF1-derived MPNST cell proliferation by weakened BDNF/TrkB/ERK signalling. Targeting NF1-derived MPNSTs with TrkB inhibitors, or in combination with ERK inhibitors, may be a novel therapeutic strategy for clinical trials. |
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