Department of Neurology, Jining NO.1 People's Hospital.
Biol Pharm Bull. 2020;43(4):639-648. doi: 10.1248/bpb.b19-00818.
Sema3C has been reported to promote glioma stem cells self-renewal and glioblastoma growth. However, the prognostic value and the regulatory mechanism for its abnormal expression in glioma remain poorly understood. In the current study, the immunohistochemistry results demonstrated that Sema3C was overexpressed in 169 of 216 (78.2%) interpretable glioma patients compared with 3 of 15 (20.0%) interpretable non-neoplastic brain cases (p = 0.0001). Sema3C overexpression was significantly associated with histologic type (p = 0.008), high Ki67 labeling index (p = 0.02), tumor grade (p = 0.002) and wild type IDH1 (p = 0.0001). Importantly, its overexpression predicts the shorter overall survival of glioma patients (p = 0.0017), especially the ones with high grade (p = 0.0124). Functionally, Sema3C silencing significantly reduced the proliferation and invasion of glioma cells, indicating an oncogenic role of Sema3C in glioma in vitro. To elucidate the reason accounting for its overexpression, it is identified miR-142-5p as a tumor suppressor that directly targets Sema3C in glioma cells. miR-142-5p and Sema3C were co-regulators of epithelial-mesenchymal transition. Clinically, miR-142-5p expression was conversely related with Sema3C expression in glioma samples. Together, we identified that Sema3C could promote the progression of glioma and its expression was negatively regulated by miR-142-5p in vitro. Thus, the miR-142-5p-Sema3C axis plays importantly in glioma and holds potential to be therapeutic targets as well.
Sema3C 已被报道可促进神经胶质瘤干细胞自我更新和神经胶质瘤的生长。然而，其在神经胶质瘤中异常表达的预后价值及其调控机制仍知之甚少。在本研究中，免疫组织化学结果表明，与 15 例可解释的非肿瘤性脑病例中的 3 例（20.0%）相比，169 例可解释的神经胶质瘤患者中有 169 例（78.2%） Sema3C 过表达（p=0.0001）。Sema3C 过表达与组织学类型（p=0.008）、高 Ki67 标记指数（p=0.02）、肿瘤分级（p=0.002）和野生型 IDH1（p=0.0001）显著相关。重要的是，其过表达预测神经胶质瘤患者的总生存时间较短（p=0.0017），尤其是高级别患者（p=0.0124）。功能上，Sema3C 沉默显著降低了神经胶质瘤细胞的增殖和侵袭，表明 Sema3C 在体外具有致癌作用。为了阐明其过表达的原因，发现 miR-142-5p 作为一种肿瘤抑制因子，可直接靶向神经胶质瘤细胞中的 Sema3C。miR-142-5p 和 Sema3C 是上皮-间充质转化的共同调节因子。临床上，miR-142-5p 在神经胶质瘤样本中的表达与 Sema3C 的表达呈负相关。总之，我们确定 Sema3C 可以促进神经胶质瘤的进展，其表达在体外受 miR-142-5p 的负调控。因此，miR-142-5p-Sema3C 轴在神经胶质瘤中具有重要作用，并有可能成为治疗靶点。
