Department of Medical Oncology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
Int J Med Sci. 2021 Oct 15;18(16):3768-3779. doi: 10.7150/ijms.58415. eCollection 2021.
Neuron specific enolase (NSE) is a specific biomarker for SCLC. However, the biological roles and aberrant expression of NSE in SCLC have not been well illustrated. The expression of NSE, miR-93-5p and LINC00657 in SCLC tissues and cell lines were detected using real time quantitative PCR (qRT-PCR) or immunohistochemistry. CCK8 assay was performed to detect cell proliferation. Cell migration and invasion capabilities were investigated by transwell assay. Epithelial-mesenchymal transition (EMT) process was verified by detecting epithelial marker E-cadherin and mesenchymal marker N-cadherin. The direct interactions between miR-93-5p and NSE or LINC00657 were predicted by bioinformatics tools and verified using dual luciferase reporter assay. Upregulated expression of NSE in SCLC tumor tissues were positively associated with advanced tumor stage, distant metastasis and poor overall survival. Overexpression of NSE promoted cell proliferation, migration, invasion and EMT in SCLC cells, while silence of NSE inhibited these effects. Mechanically, NSE expression was positively correlated with LINC00657, and negatively correlated with miR-93-5p. Moreover, NSE was positively regulated by LINC00657 through sponging of miR-93-5p. LINC00657 and miR-93-5p promoted SCLC cell migration, invasion and EMT by NSE-mediated manner. Overall, our study revealed a novel role of NSE in SCLC. NSE was positively regulated by LINC00657 through competitively interacting with miR-93-5p, which may be potential targets for SCLC patients.
神经元特异性烯醇化酶（NSE）是小细胞肺癌（SCLC）的特异性生物标志物。然而，NSE 在 SCLC 中的生物学作用和异常表达尚未得到充分阐明。采用实时定量 PCR（qRT-PCR）或免疫组织化学检测 SCLC 组织和细胞系中 NSE、miR-93-5p 和 LINC00657 的表达。通过 CCK8 assay 检测细胞增殖。通过 Transwell assay 检测细胞迁移和侵袭能力。通过检测上皮标志物 E-钙黏蛋白和间充质标志物 N-钙黏蛋白验证上皮-间充质转化（EMT）过程。通过生物信息学工具预测 miR-93-5p 与 NSE 或 LINC00657 的直接相互作用，并通过双荧光素酶报告基因 assay 进行验证。在 SCLC 肿瘤组织中上调的 NSE 表达与晚期肿瘤分期、远处转移和不良总生存期呈正相关。NSE 的过表达促进了 SCLC 细胞的增殖、迁移、侵袭和 EMT，而 NSE 的沉默抑制了这些作用。机制上，NSE 表达与 LINC00657 呈正相关，与 miR-93-5p 呈负相关。此外，NSE 通过竞争性结合 miR-93-5p 被 LINC00657 正向调控。LINC00657 和 miR-93-5p 通过 NSE 介导的方式促进 SCLC 细胞迁移、侵袭和 EMT。总的来说，我们的研究揭示了 NSE 在 SCLC 中的新作用。NSE 通过与 miR-93-5p 竞争性结合，被 LINC00657 正向调控，这可能是 SCLC 患者的潜在靶点。
