Zhang Dainan, Ma Shunchang, Zhang Chuanbao, Li Peiliang, Mao Beibei, Guan Xiudong, Zhou Wenjianlong, Peng Jiayi, Wang Xi, Li Shaomin, Jia Wang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Front Oncol. 2021 Mar 12;11:566492. doi: 10.3389/fonc.2021.566492. eCollection 2021.
MicroRNAs (miRNAs) are involved in human glioblastoma (GB). MiR-935 has been reported to have both tumor-inhibiting and tumorigenesis effects, but its role in GB remains unclear. Because of the high mortality and morbidity associated with the malignancy of GB, a deeper understanding of the molecular crosstalk that occurs in GB is needed to identify new potential targets for treatment. At present, the mechanism of GB at the molecular level is not fully understood. With the aid of bioinformatic analysis, miR-935 was significantly downregulated in GB, and it presented a poorer outcome. In the glioma cell line and in the nude mice model, the miR-935 inhibited cell proliferation by modulating cell circles and . Then, the target genes of miR-935 were analyzed by using the online database, and the direct binding was tested with a luciferase analysis. FZD6 was found to be the direct target of miR-935. The effect of miR-935 was recovered by the overexpression of FZD6 . In addition, the negative correlation of miR-935 and the expression of FZD6 were confirmed in our clinical samples, and the expression of FZD6 has a strong correlation with tumor malignancy and prognosis. This study showed that miR-935 directly inhibited the expression of FZD6 and inhibited the cell proliferation, thereby suppressing the development of GB, suggesting that miR-935 is a cancer suppressor miRNA and may become a prognostic biomarker or a promising potential therapeutic target for human GBs.
微小RNA（miRNA）与人类胶质母细胞瘤（GB）有关。据报道，miR-935具有肿瘤抑制和肿瘤发生两种作用，但其在GB中的作用仍不清楚。由于GB恶性肿瘤相关的高死亡率和高发病率，需要更深入地了解GB中发生的分子相互作用，以确定新的潜在治疗靶点。目前，GB在分子水平上的机制尚未完全了解。借助生物信息学分析，miR-935在GB中显著下调，且预后较差。在胶质瘤细胞系和裸鼠模型中，miR-935通过调节细胞周期抑制细胞增殖。然后，利用在线数据库分析miR-935的靶基因，并用荧光素酶分析检测直接结合情况。发现FZD6是miR-935的直接靶标。FZD6的过表达恢复了miR-935的作用。此外，在我们的临床样本中证实了miR-935与FZD6表达的负相关，且FZD6的表达与肿瘤恶性程度和预后密切相关。本研究表明，miR-935直接抑制FZD6的表达并抑制细胞增殖，从而抑制GB的发展，提示miR-935是一种抑癌miRNA，可能成为人类GB的预后生物标志物或有前景的潜在治疗靶点。
