Liu Jing, Xu Yanwen, Tang Han, Liu Xia, Sun Yanhua, Wu Tingting, Gao Ming, Chen Peng, Hong Huixia, Huang Guodong, Zhou Yanxia
Department of Pathology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518000, P.R. China.
Translational Medicine Institute, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518000, P.R. China.
Exp Ther Med. 2023 Jul 6;26(2):397. doi: 10.3892/etm.2023.12096. eCollection 2023 Aug.
The present study investigated the expression level of microRNA (miR)-137 in glioma tissues and cell lines and explored its potential diagnostic significance as well as its function effects on glioma cells. miR-137 expression level was detected in glioma tissues using hybridization, and in glioma cell lines using reverse transcription-quantitative PCR (RT-qPCR). The diagnostic significance of miR-137 in glioma was assessed using receiver operating characteristic curve analyses. Quantibody Human Inflammation Array 1 was used to evaluate the impact of ectopic miR-137 expression on release of cytokines in glioma cell lines. IL-13, TNF-α and IFN-γ levels were detected using ELISA. To confirm that sphingosine kinase 2 (SPHK2) is a target of miR-137, RT-qPCR, western blot analysis and dual-luciferase assay were adopted. The results demonstrated that miR-137 expression was downregulated in both glioma tissues and cell lines. Downregulation of miR-137 was significantly associated with high grade gliomas. Additionally, it was found that overexpression of miR-137 reduced IL-13, but promoted TNFα and IFN-γ production. SPHK2 knockdown inhibited IL-13 release, promoted TNF-α and IFN-γ production. SPHK2 was a direct target of miR-137. Collectively, the results of the present study indicated that miR-137 expression plays a tumor-suppressive role in glioma. It is downregulated in glioma and may promote M1-type TAMs polarization, and may be a diagnostic biomarker and potential therapeutic strategy for glioma treatment in the future.
本研究调查了微小RNA（miR）-137在胶质瘤组织和细胞系中的表达水平，探讨了其潜在的诊断意义以及对胶质瘤细胞的功能影响。采用杂交法检测胶质瘤组织中的miR-137表达水平，采用逆转录定量聚合酶链反应（RT-qPCR）检测胶质瘤细胞系中的miR-137表达水平。使用受试者工作特征曲线分析评估miR-137在胶质瘤中的诊断意义。使用定量抗体人炎症阵列1评估异位miR-137表达对胶质瘤细胞系中细胞因子释放的影响。使用酶联免疫吸附测定（ELISA）检测白细胞介素-13（IL-13）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）水平。为了证实鞘氨醇激酶2（SPHK2）是miR-137的靶标，采用了RT-qPCR、蛋白质免疫印迹分析和双荧光素酶测定。结果表明，miR-137在胶质瘤组织和细胞系中均表达下调。miR-137的下调与高级别胶质瘤显著相关。此外，发现miR-137的过表达降低了IL-13，但促进了TNF-α和IFN-γ的产生。敲低SPHK2抑制了IL-13的释放，促进了TNF-α和IFN-γ的产生。SPHK2是miR-137的直接靶标。总体而言，本研究结果表明，miR-137表达在胶质瘤中发挥肿瘤抑制作用。它在胶质瘤中表达下调，可能促进M1型肿瘤相关巨噬细胞极化，并且可能是未来胶质瘤治疗的诊断生物标志物和潜在治疗策略。
