Chen Wangsheng, Hong Lan, Hou Changlong, Wang Yibin, Wang Fei, Zhang Jianhua
Department of Radiology, Hainan General Hospital/Hainan Hospital of Hainan Medical University, Haikou, 570311 China.
Department of Gynecology, Hainan General Hospital/Hainan Hospital of Hainan Medical University, Haikou, 570311 China.
Cancer Cell Int. 2020 Sep 29;20:469. doi: 10.1186/s12935-020-01528-w. eCollection 2020.
MicroRNAs (miRNAs) are important regulators for cancer cell proliferation. miR-585 has been shown to inhibit the proliferation of several types of cancer, however, little is known about its role in human glioma cells.
miR-585 levels in human glioma clinical samples and cell lines were examined by quantitative real-time PCR (qRT-PCR) analysis. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and EdU incorporation assays in vitro. For in vivo investigations, U251 cells were intracranially inoculated in BALB/c nude mice and xenografted tumors were visualized by magnetic resonance imaging (MRI).
miR-585 expression is downregulated in human glioma tissues and cell lines compared with non-cancerous counterparts. Additionally, miR-585 overexpression inhibits and its knockdown promotes human glioma cell proliferation in vitro. Moreover, miR-585 overexpression also inhibits the growth of glioma xenografts in vivo, suggesting that miR-585 may act as a tumor suppressor to inhibit the proliferation of human glioma. Furthermore, miR-585 directly targets and decreases the expression of oncoprotein murine double minute 2 (MDM2). More importantly, the restoration of MDM2 via enforced overexpression markedly rescues miR-585 inhibitory effect on human glioma cell proliferation, thus demonstrating that targeting MDM2 is a critical mechanism by which miR-585 inhibits human glioma cell proliferation.
Our study unveils the anti-proliferative role of miR-585 in human glioma cells, and also implicates its potential application in clinical therapy.
微小RNA（miRNA）是癌细胞增殖的重要调节因子。已表明miR-585可抑制多种类型癌症的增殖，然而，其在人类胶质瘤细胞中的作用鲜为人知。
通过定量实时PCR（qRT-PCR）分析检测人类胶质瘤临床样本和细胞系中miR-585的水平。体外使用细胞计数试剂盒-8（CCK-8）和EdU掺入试验测量细胞增殖。对于体内研究，将U251细胞颅内接种到BALB/c裸鼠中，并通过磁共振成像（MRI）观察异种移植瘤。
与非癌对应物相比，人类胶质瘤组织和细胞系中miR-585表达下调。此外，miR-585过表达抑制，其敲低促进体外人类胶质瘤细胞增殖。此外，miR-585过表达还抑制体内胶质瘤异种移植瘤的生长，表明miR-585可能作为肿瘤抑制因子抑制人类胶质瘤的增殖。此外，miR-585直接靶向并降低癌蛋白小鼠双微体2（MDM2）的表达。更重要的是，通过强制过表达恢复MDM2可显著挽救miR-585对人类胶质瘤细胞增殖的抑制作用，从而证明靶向MDM2是miR-585抑制人类胶质瘤细胞增殖的关键机制。
我们的研究揭示了miR-585在人类胶质瘤细胞中的抗增殖作用，并暗示了其在临床治疗中的潜在应用。
